Category Archives: Genetics

Fulgent Genetics (NASDAQ:FLGT Get Rating) was upgraded by Zacks Investment Research from a hold rating to a buy rating in a note issued to investors on Tuesday, Zacks.com reports. The firm currently has a $65.00 price target on the stock. Zacks Investment Researchs price objective indicates a potential upside of 18.20% from the stocks current price.

According to Zacks, Fulgent Genetics, Inc. is a technology company. It provide genetic testing services to physicians with clinically actionable diagnostic information. The Companys technology platform integrates data comparison and suppression algorithms, adaptive learning software, advanced genetic diagnostics tools and integrated laboratory process which serves primarily to hospitals and medical institutions. Fulgent Genetics, Inc. is headquartered in Temple City, California.

Several other research firms have also recently weighed in on FLGT. Oppenheimer decreased their target price on Fulgent Genetics from $141.00 to $125.00 and set an outperform rating for the company in a research note on Tuesday, January 25th. StockNews.com began coverage on Fulgent Genetics in a research note on Thursday, March 31st. They set a hold rating for the company. Finally, Piper Sandler boosted their target price on Fulgent Genetics from $80.00 to $85.00 in a research note on Tuesday, March 1st.

Fulgent Genetics (NASDAQ:FLGT Get Rating) last announced its quarterly earnings data on Wednesday, February 23rd. The company reported $3.34 earnings per share (EPS) for the quarter, beating the consensus estimate of $2.66 by $0.68. The business had revenue of $251.67 million during the quarter, compared to analysts expectations of $191.10 million. Fulgent Genetics had a return on equity of 51.21% and a net margin of 51.12%. The businesss quarterly revenue was down 14.7% compared to the same quarter last year. During the same quarter last year, the business posted $6.12 EPS. On average, analysts anticipate that Fulgent Genetics will post 7.3 EPS for the current year.

In other Fulgent Genetics news, CFO Paul Kim sold 454 shares of the businesss stock in a transaction that occurred on Thursday, March 3rd. The stock was sold at an average price of $56.31, for a total value of $25,564.74. The sale was disclosed in a legal filing with the Securities & Exchange Commission, which is available at this link. 29.50% of the stock is currently owned by insiders.

A number of hedge funds and other institutional investors have recently modified their holdings of FLGT. Spire Wealth Management increased its holdings in shares of Fulgent Genetics by 10.8% in the fourth quarter. Spire Wealth Management now owns 1,375 shares of the companys stock valued at $138,000 after purchasing an additional 134 shares during the period. Raymond James Financial Services Advisors Inc. increased its holdings in shares of Fulgent Genetics by 0.7% in the third quarter. Raymond James Financial Services Advisors Inc. now owns 20,322 shares of the companys stock valued at $1,828,000 after purchasing an additional 146 shares during the period. Maryland State Retirement & Pension System increased its holdings in shares of Fulgent Genetics by 2.4% in the fourth quarter. Maryland State Retirement & Pension System now owns 7,730 shares of the companys stock valued at $778,000 after purchasing an additional 180 shares during the period. First Foundation Advisors increased its holdings in shares of Fulgent Genetics by 4.0% in the third quarter. First Foundation Advisors now owns 4,728 shares of the companys stock valued at $425,000 after purchasing an additional 182 shares during the period. Finally, Dimensional Fund Advisors LP increased its holdings in shares of Fulgent Genetics by 3.4% in the fourth quarter. Dimensional Fund Advisors LP now owns 5,527 shares of the companys stock valued at $556,000 after purchasing an additional 182 shares during the period. Institutional investors own 38.33% of the companys stock.

About Fulgent Genetics (Get Rating)

Fulgent Genetics, Inc, together with its subsidiaries, provides COVID-19, molecular diagnostic, and genetic testing services to physicians and patients in the United States and internationally. The company offers genetic tests comprising Focus and Comprehensive oncology panels tests; Beacon carrier screening panels test for inherited conditions; solid tumor molecular profiling for somatic cancer testing; rapid whole genome testing for children in NICU and PICU; newborn genetic analysis panel; single front-line test to detect ataxia-related variants and repeat expansions through sequencing; picture genetics, a patient-initiated genetic testing; whole exome and clinical exome panel tests; whole genome, mutation, and repeat expansion testing services, as well as research service tests.

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Fulgent Genetics (NASDAQ:FLGT) Lifted to Buy at Zacks Investment Research - Defense World

The year 2007 was heart-wrenching for Houston native Ashley Dedmon. Her mother, Lynn Armstrong, died of stage IV metastatic breast cancer at the age of 52.

She later discovered the disease was a silent killer no one in her family had discussed.

Breast cancer aggressively attacked three generations of women and I didnt know why they all succumbed to the disease, she says. I needed to get to work and ask questions to protect my health.

Now is the ideal time to channel Dedmons energy for National Minority Health Month to do the work to learn the impact of genetics. Each exquisite strand of DNA shares a code about health risks that, if unknown or untreated, could have a significant effect on ones life and lifespan.

Months after her mothers death, Dedmons father was diagnosed with prostate cancer. He had surgery to remove it and now lives cancer-free. Paralyzed by fear that she could be the next family member to be diagnosed with cancer, she put her faith in God and made an important decision to break a familial cycle.

I underwent genetic testing, as recommended by my gynecologist, and at the age of 22, I found out I carry the BRCA2 gene mutation, she says. That means I am at high risk for breast and ovarian cancers and have an elevated risk for other cancers. I learned I inherited it from my mother.

Dedmon had her first mammogram at the age of 22 and began seeing a high-risk oncologist to monitor her breast and ovarian health.The next decade of her life included annual screenings, marrying the love of her life, Cameron and giving birth to two healthy daughters, Ava and Callie.

During that season of my life, I saw myself repeating the same patterns as my mom, by putting everyone and everything before my health, she recalls. But I knew better and was educated and armed with information to preserve my life.

In December 2016, at the age of 31, she underwent a bilateral prophylactic mastectomy, or preventative double mastectomy. In laymans terms, the removal of both breasts. The procedure has been shown to reduce the risk of breast cancer by at least 95 percent in women who have a mutation in the BRCA1 or BRCA2 gene and by up to 90 percent in women who have a strong family history of breast cancer according to the National Cancer Institute.

Altovise Ewing, PhD, LCGC, is a health equity strategist and genetic counselor who amplifies efforts around genetic testing for African-Americans. Ewing reports that across the genetics research continuum, people of color are underrepresented at the participant, clinician and investigator levels.

Genetic counseling and testing are services that can help patients and families better understand their risk and management options for various conditions, Ewing explains. Because the Black population is disproportionately impacted and burdened by multiple diseases, genetics services may serve as one of the tools in the toolkit to help prevent, treat and manage disease.

Chronic diseases that affect African Americans at a higher rate include cancer, diabetes and heart disease.Ewing explains that although genetics alone does not tell the entire story, it can be a very important clue that opens the door to a new chapter of more precise, safe, and efficient care management, not only for an individual but also for a family.

I talk to my girls about our family history of cancer and heart diseases, Dedmon says. I normalize the conversation at a very young age so that when they become young adults, they are educated, equipped and empowered to make their decisions about genetic testing and managing their health.

Here are practical steps one can take to determine genetic makeup:

Dedmon, now 36, educates audiences nationwide about breast cancer prevention and genetic testing in partnership with organizations such as Penn Medicines Basser Center for BRCA Black and BRCA Initiative, The Tigerlily Foundation, FORCE and The WISDOM Study to stress the importance of knowing ones genetic status.

Its especially important to her to educate younger generations.

Im a believer, and the Bible says faith without works is dead, so I needed to get to work, ask questions and protect my health, she says. I am confident I made the best health decision for me, my girls and my future.

Lyndsay Levingston is a multimedia maven, breast cancer survivor and founder of SurviveHER, a breast cancer awareness nonprofit organization whose mission is to inform, inspire and empower year-round.

TOPICS: Cancer health and wellness National Minority Health Month

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How A Genetic Test Saved This Black Womans Life - Essence

(Boston)Camron D. Bryant, PhD, associate professor of pharmacology and psychiatry at Boston University School of Medicine (BUSM), has been awarded a five-year, $3.5 million grant from the National Institutes of Health National Institute on Drug Abuse, which will help fund his latest research on the various aspects of drug addiction, including genetics. Kathleen Kantak, PhD, professor of psychological and brain sciences at Boston University, is a multi-principal investigator recipient of this award.

Concurrent with the opioid epidemic, cocaine use disorder (CUD) and cocaine-related deaths have skyrocketed over the past decade. Despite a well-documented genetic component, the genetic factors underlying risk versus protection from CUD remain largely unknown. At the moment, there are no FDA-approved drugs for CUD; thus, a better understanding of the risk factors for CUD could ultimately lead to new therapeutics, explains Bryant.

Kantak and Bryant recently identified robust differences between two genetically similar experimental models that predict risk for cocaine addiction, including impulsive- and compulsive-like behaviors.

Using this award, they will apply quantitative genetics toward these behavioral measures and toward gene expression analysis (RNA, protein) to identify the causal genes underlying differences in susceptibility to these behaviors. According to Bryant, the fact that these model strains are nearly identical at the genetic level will facilitate the pace of gene discovery.

Bryant completed his undergraduate degree in psychology at the University of Illinois, Urbana-Champaign and earned his PhD in neuroscience from UCLA in 2006 where he focused on signaling mechanisms and Pavlovian-conditioned properties of opioid adaptive behaviors. He completed positions as a postdoc and research associate in genetics at the University of Chicago prior to joining the department of pharmacology at BUSM in 2012.

He has received numerous awards including the Achievement Award for College Scientists (ARCS), the International Behavioural and Neural Genetics Society (IBANGS) Outstanding Young investigator Award for Postdocs, the IBANGS Early Career Scientist Award, and the American College of Neuropsychopharmacology (ACNP) Travel Award. He is currently the president of IBANGS, a full member of ACNP and serves as a frequent ad hoc reviewer for several peer-reviewed journals in his field including Genes, Brain and Behavior, Psychopharmacology, PLoS Genetics, Neuropsychopharmacology, Communications Biology, and Addiction Biology. He currently a permanent member on NIH Study section and is the Associate Director for the Center for Systems Neuroscience at Boston University.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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BU doc receives NIH funding to study addiction-related behavior - EurekAlert

Gregor Mendel was born two hundred years ago in 1822 in a village in Silecia, then part of the Austrian Empire, almost 200 Km north of Brno in todays Czechia. At the age of 21 he entered the abbey first as a friar and later becoming abbot. While he was devoted to his religion, he was also devoted to science and being at the abbey gave him time to pursue his interest in biology. He conducted experiments with peas and other plants, and through careful observation and record-keeping came up with a theory of inheritance which forms the basis of modern biology. Pauline Newman visits the abbey in the old centre of Brno and the Mendel Museum there. She reports on the life of Gregor Mendel, how he was able to pursue his biological observations and how his results and ideas fitted with other thoughts of the time, particularly those of Charles Darwin.

GuestsBlankaKovDirector, Mendel MuseumMasaryk UniversityBrno, Czechia

Tom McLeishProfessor of Natural PhilosophyDepartment of PhysicsUniversity of YorkEngland UK

Daniel FairbanksProfessor of BiologyUtah Valley UniversityOrem, Utah USA

Ard LouisProfessor of Theoretical PhysicsUniversity of OxfordOxford UK

ReporterPauline Newman

PresenterRobyn Williams

ProducerDavid Fisher

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Celebrating Gregor Mendel the father of genetics - The Science Show - ABC News

High blood pressure means the force of blood flowing through your arteries is greater than it should be. If not controlled, it could damage your blood vessels and cause other health problems.

High blood pressure (hypertension) tends to be a condition we associate with being too sedentary or getting older. But high blood pressure can also be a genetic condition, affecting people who are otherwise fit and healthy.

A parent with high blood pressure can pass along a gene to a child, raising that persons risk of developing hypertension one day. Familial hypertension may also result from a family lifestyle that includes high blood pressure risk factors, such as smoking or an unhealthy diet.

Blood pressure is the force of circulating blood against the inner wall of your arteries. Its measured in millimeters of mercury (mm Hg) and is presented as two numbers:

According to the American Heart Association, healthy blood pressure is a systolic pressure of less than 120 mm Hg and a diastolic pressure of less than 80 mm Hg. This is a blood pressure of less than 120/80 mm Hg.

If your blood pressure is higher than that, doctors consider you to have elevated blood pressure or stage 1 or 2 hypertension.

Risk factors for high blood pressure include a family history of hypertension, as well as:

What makes high blood pressure so dangerous is that it can exist for a long time without presenting any obvious symptoms. Measuring your blood pressure is the only way to know if you have hypertension.

In extreme cases, when blood pressure exceeds 180/120 mm Hg, you have a medical emergency known as a hypertensive crisis. Symptoms can include:

Research from 2017 suggests that high blood pressure results from a combination of factors, including genetic, environmental, and behavioral components.

Unlike some diseases with only one or a few genes as risk factors, familial hypertension can result from variations in hundreds of different genes, according to a 2019 study of more than 750,000 individuals. This makes it difficult to pinpoint specific genes that could be treatment targets.

The Centers for Disease Control and Prevention (CDC) also notes that families may affect a persons hypertension risk because of the home environment.

Smoking or even breathing in secondhand smoke can raise blood pressure risks. A diet high in sodium and saturated fat may also cause a blood pressure increase. If physical activity and good sleeping habits arent part of a family dynamic, blood pressure can also be negatively affected.

Monogenic hypertension refers to blood pressure caused by one genetic variant inherited from a parent. Monogenic hypertension accounts for about 30 percent of hypertension cases. Most of those are associated with imbalances of electrolytes, such as potassium.

There are several types of monogenic hypertension syndromes, each with a unique set of origins and symptoms. These include:

Knowing about your family medical history is important for many reasons. A history of certain cancers, for example, may determine when you get screened for those cancers. If high blood pressure runs in your family, its important to share this information with your doctor and regularly monitor your blood pressure.

One way to organize information about your family health history, as well as your own, is to use My Family Health Portrait, an online tool created by the National Institutes of Health. You can gather your family medical history, share it with other relatives, and learn about your risk levels for conditions that tend to run in families.

If your blood pressure is currently at a healthy level, you can make several key lifestyle adjustments to lower the odds of it rising too much. If your blood pressure is higher than usual, these steps, along with medications, may help you bring it back down to a healthy range:

The National Heart, Lung, and Blood Institute developed the Dietary Approaches to Stop Hypertension (DASH) eating plan as a heart-healthy eating strategy.

This plan focuses on managing blood pressure by emphasizing fruits, vegetables, whole grains, lean proteins, and sodium reduction. Its also flexible enough to let people enjoy many of their favorite foods.

Sufficient sleep is essential to good overall health, especially for brain and heart function. Blood pressure is especially susceptible to problems related to poor sleep.

A 2022 study suggests that frequent sleep disturbances and short sleep, or less than 5, 6, or 7 hours, can contribute to hypertension.

Taking steps to improve sleep duration and quality may improve more than just your cardiovascular health. It can also improve your mood, concentration, energy, metabolism, and more.

Hypertension is a major risk factor for cardiovascular disease, the leading cause of death in the United States. High blood pressure is also a leading cause of stroke and a risk factor for chronic kidney disease and other health problems.

If your family medical history includes high blood pressure, start taking steps to lower your risk through heart-healthy behaviors. Even if you dont know your family history or dont have a close relative with hypertension, its still important to take steps to keep your blood pressure under control.

Theres a variety of anti-hypertensive medications that can help. But these medications dont take the place of a healthy diet, exercise, and getting plenty of sleep to help maintain a healthy blood pressure.

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Familial Hypertension: The Genetics of High Blood Pressure - Healthline

Introduction

Cancer has been one of the leading causes of human death. According to estimates, more than 220 thousand new cases of lung cancer will occur in the United States in 2020.1 In general, lung cancer is subdivided into two categories, of which small cell lung cancer (SCLC) represents about 1315%. At diagnosis, about 80% of patients with SCLC are in an advanced stage and cannot undergo surgery.2

SCLC is a highly heterogeneous malignant neuroendocrine tumor.3 Small cell transformation has been demonstrated to be one of the ways in which non-small cell lung cancer (NSCLC) develops resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), leading to a poor prognosis.4 Although TP53 and RB1 are tumor suppressor genes with high incidence, few genetic driver events have been reported.5 Recent evidence reveals that immune checkpoint inhibitors (ICIs) and specifically programmed death ligand 1 inhibitors combined with standard platinum/etoposide can enhance progression-free survival with minimal adverse effects in patients with extensive SCLC.6,7 Furthermore, recent evidence shows that co-stimulatory B7-H3 may act as an independent prognostic indicator for SCLC cases, which might provide a theoretical basis for subsequent research targeting B7-H3.8,9

FOXM1 is crucial for SCLC tumorigenesis and is associated with a poor prognosis. After standard chemotherapy, patients with high FOXM1 expression had shorter progression-free survival compared to those with low FOXM1 expression (3.90 vs 8.69 months).10 In vitro experiments and experiments on xenograft (PDX) models derived from SCLC patient-derived xenograft reveal that pharmacological inhibition of DHODH can suppress the cell viability.11 Therefore, in SCLC treatment, DHODH has been a promising target.

SCLC is prone to develop chemoresistance due to its intratumoral heterogeneity.12 Despite recent advances, SCLC remains the most lethal lung cancer with limited therapeutic options. Studies report that patients with SCLC have a poor prognosis, except for a minimal number of early-stage cases.13

Accumulated studies demonstrate that SCLC is a highly heterogeneous tumor, although fewer genetic colonies have been reported comparison with NSCLC. Transcriptomic analyses reveal four different molecular subtypes, including SCLC-A driven by the transcription factor ASCL1, SCLC-N driven by NEUROD1, SCLC-Y by YAP1 and SCLC-P by POU2F3,14 allowing for more targeted therapeutic approaches. Subsequent studies confirmed that a unique YAP1 subtype did not exist, and an inflamed subtype of SCLC (SCLC-I) was recently proposed to replace YAP1 subtype.15 Although SCLC-I subtype experienced the greatest benefit from immune checkpoint inhibitor therapy, the clinical significance of this molecular subtyping in guiding treatment and estimating prognosis remains limited to other standard SCLC treatments.

The development of next-generation sequencing technology (NGS) has led to the identification of many genetic alterations in SCLC, including TP53 and RB1 inactivation and frequent chromosomal abnormalities (deletion 3p).16 In addition to the inactivated Notch pathway, MYC family amplification has a high incidence.17 Few druggable targeted molecules can be used in clinical practice.18 Currently, NGS is widely employed in routine clinical practice of non-small cell lung cancer to assist in therapeutic options and prognosis evaluation. Therefore, it is essential to investigate the genetic characteristics of SCLC and their clinical implications.

In this study, 18 cases of pathologically proven SCLC cases were sequenced using a panel of 520 cancer-related genes. The average median sequencing depth of the samples was 1260x. The average median q30 ratio of the samples was 91%, and all samples are qualified. Analyzing the sequencing results and pathological data revealed some genetic variants with distinctive characteristics.

SCLC presents a distinctive mutation spectrum compared to adenocarcinoma. In our cohorts, results reveal 72% cooccurring TP53/RB1 mutations. Furthermore, in the samples of small cell lung cancer, the core 8 gene was not detected. In SCLC, the frequency of gene mutations is significantly lower than in adenocarcinoma. The mutation frequency of Rb1, MSH6, KDR, IL7R, ATRX, EPHB1, PDGFRA and KIT in SCLC is markedly higher than those in lung squamous cell carcinoma. Due to the small sample size, it might be affected by some random factors.

Patients diagnosed with SCLC at Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, were enrolled in this study after obtaining informed consent. Biopsy specimens of advanced stage SCLC were obtained from the Department of Pathology Affiliated Cancer Hospital of Zhengzhou University. The study protocols were approved by the institutional ethics review board (Ethics Review Committee, Zhengzhou University). While collecting specimens for analysis, we complied with the declaration of Helsinki (2013 Edition) and relevant regulations. Additionally, the clinical characteristics were recovered in this research.

DNA extraction and targeted sequencing were performed in Burning Rock Biotech as described in the previous protocol.19,20 In brief, formalin-fixed, paraffin-embedded (FFPE) specimens were used for DNA extraction through QIAamp DNA kit (Qiagen, Germany). Subsequently, DNA purification, hybridization and amplification were performed. Target capture was conducted through a commercial 520 genes panel (OncoScreen Plus). The quality of fragments was determined using a Bioanalyzer 2100 (Agilent Technologies, USA). Finally, the samples were sequenced via the platform of nextseq 500 (Illumina, Inc., USA).

The reference genome Hg19 was used through Burrows-Wheeler Aligner version 0.7.10.21 Subsequently, sequence alignment and variant calling were performed through programs including varscan version 2.4.3 and the genome analysis tool kit version 3.2.22 The genes variants were annotated with ANNOVAR.23 The structural variations (SVs) were analyzed using Factera version 1.4.3.24

It should count as mutations that non-synonymous single nucleotide variants (SNVs) and indels in the coding sequences and two adjacent base pairs around these regions, while hot mutation, copy number variations (CNVs), structural variations (SVs), and SNPs were excluded.

The size of coding sequences required to estimate TMB is 1.003 MB in the 520 gene panel. The MB per patient was calculated using the following formula.

Table 1 lists the clinical and pathological information of SCLC patients. Prospective follow-up was conducted through routine hospital visits or telephone calls. Once every three months, trained medical staff made telephone calls to patients or their family members until death or the last follow-up. The follow-up data of this cohort is included in the Supplementary Materials. Overall survival (OS) was estimated from the day of SCLC diagnosis to the day of death from any cause and was analyzed using KaplanMeier estimates and Log rank test. The correlations between categorical variables were calculated using Chi-squared and Fishers exact tests. Statistical analyses were performed using SPSS23.0, and P 0.05 was considered statistically significant.

Table 1 Clinicopathological Characteristics of the 18 SCLC Patients

Capture-based targeted sequencing was performed by Burning Rock Biotech, Guangzhou, China. The average median sequencing depth of the samples was 1260x, consistent with expectations. The average median q30 ratio of the samples was 91%, and all samples were qualified (Supplementary Figure 1). The deletion of the tumor suppressor genes TP53 and RB1 has long been recognized as a common mutation in SCLC. Out of 18, 13 patients showed a co-mutation of TP53 and RB1, reaching a mutation rate of 72%, and the remaining five patients were found with wild-type RB1 as displayed in Figure 1A. Other frequent mutant genes are LRP1B, FAT3, KMT2D, KDR, PTEN, SPTA1, MSH6, Bcl6, EPHB1, etc. Figure 1B illustrates the distribution of identified mutations in SCLC.

Figure 1 Mutation landscape of SCLC. (A) Genomic alteration profiling. X axis is specific specimens and Y axis is the detected mutations for a different gene. The percentage of mutation of a specific gene in total patients. (B) Distribution of mutations in SCLC.

The genetic alteration observed in our cohort was in accordance with the SCLC database of Burning Rock Biotech (RS_SCLC) (Figure 2A). Figure 2A includes genes detected in at least three samples. The gene mutation frequency in this cohort did not differ significantly from that in RS_SCLC database.

Figure 2 (A) Genetic alteration in our cohort consistent with Burning Rock Biotech SCLC database (RS_SCLC). (B) Genetic differences between SCLC and non-small cell lung cancer (NSCLC) (C). Single nucleotide variation analysis. *in (B and C) represents statistically significant differences (p < 0.05). **in (B and C) represents statistically significant differences (0.01

The genetic differences between SCLC and non-small cell lung cancer were further analyzed (Figure 2B) to explore the molecular genetic characteristics of SCLC. In comparison with NSCLC (adenocarcinoma and squamous cell carcinoma), the mutation spectrum of SCLC differed significantly from the adenocarcinoma database of Burning Rock Biotech (RS_LUAD). Neither the core eight gene nor the frequent mutations in SCLC were detected in adenocarcinomas. Compared to Burning Rock Biotechs database of squamous cell carcinoma (RS_LUSC), the mutation frequency of genes RB1, MSH6, KDR, IL7R, ATRX, EPHB1, PDGFRA, and KIT was significantly higher. Considering the small sample size, other factors might affect it.

Furthermore, a single nucleotide variation analysis revealed that C > A mutations were more frequent in SCLC, whereas C > T mutations were significantly lower, as illustrated in Figure 2C. Moreover, we analyzed the gene copy number variation (CNV) and tumor mutation burden (TMB) in our cohorts (Figure 3). There was no significant difference in gene copy number variation (CNV) between the cohorts of SCLC group and RS_LUSC group (P = 0.54). In contrast, there was a significant difference between SCLC and RS_LUAD groups (P = 0.014). In terms of tumor mutation burden (TMB), there was no significant difference between cohorts of SCLC and RS_LUSC groups (P = 0.80), whereas there was a considerable difference between SCLC and RS_LUAD groups (P = 0.003). In general, SCLC showed higher copy number amplification and TMB compared to lung adenocarcinomas.

Figure 3 Gene copy number variation (CNV) (A) and tumor mutation burden (TMB) (B) in our SCLC cohort differ from lung adenocarcinoma.

In the final analysis, we examined the association between gene mutation and clinicopathological data, including gender, smoking, specimen origins, metastasis site, progression-free survival and overall survival (Figure 4). The criteria for gene inclusion were as follows: a. genes detected in at least three samples, b. clinical factors with at least three statistics, c. baseline sample data were included for analysis. The results revealed a significant correlation between several mutant genes and clinical factors. The KaplanMeier curve showed that patients with LRP1B (Figure 5A) or MAP3K13 (Figure 5B) mutation exhibited significantly shortened PFS.

Figure 4 The correlation between mutant gene and clinicopathological data including gender, smoking, specimen origins, metastasis site, and progression free survival and overall survival. Red indicates statistically significant differences (p < 0.05).

Figure 5 KaplanMeier curve indicated that SCLC patients with LRP1B (A) or MAP3K13 (B) mutation had significantly shorter PFS. SCLC patients with MSH6 mutation had significantly longer OS (C) while OS was significantly shorter in patients with SPEN mutation (D).

Moreover, SCLC patients with MSH6 mutation had significantly longer OS (Figure 5C), while the OS decreased significantly in patients with SPEN mutation (Figure 5D). In conclusion, MSH6 mutations are associated with a better prognosis than SPEN mutations. The results of this study may help to diagnose and treat Chinese SCLC patients.

The proportion of mutant-PIK3CA was higher in patients with bone metastases (P = 0.012), and the proportion of mutant-FAT1 was higher in patients with liver metastases (P = 0.044), as displayed in Figure 6. Of 18, five patients eventually developed bone metastases; three were detected with PIK3CA mutation, while five of the patients with liver metastases were detected with FAT1 mutation. Based on these results, it can be concluded that related signaling pathways could play a role in regulating organ-specific metastasis.

Figure 6 The proportion of mutant-PIK3CA is higher in patients with bone metastases (A), the proportion of mutant-FAT1 is higher in patients with liver metastases (B).

The signaling pathways based on KEGG involved in mutant genes were analyzed (Figure 7). A pathway is deemed mutant when at least one sample has a mutation in it. Signaling pathways with statistical correlations are listed in Table 2, which requires further investigation. The results indicated that HIF1 signaling pathway, estrogen signaling pathway, chemokine signaling pathway and T cell receptor signaling pathway contributed to bone and lymph node metastasis. Additionally, signaling pathways linked to PFS and OS were identified, and these findings may provide genetic explanations for clinicopathological features.

Table 2 The Clinical Factors are Associated with Signaling Pathway Based on KEGG Pathway to Some Extent

Figure 7 The correlation between signaling pathways involved in mutant genes (based on KEGG pathway) and clinicopathological data including gender, smoking, specimen origins, metastasis site, and progression free survival and overall survival. Red indicates statistically significant differences (p < 0.05).

SCLC in the early stages is sensitive to radiotherapy and chemotherapy. In most patients, satisfactory treatment results cannot be achieved due to the diseases early progression, recurrence, and chemotherapy resistance. Despite recent advances in SCLC, even on standard platinum-containing two-drug chemotherapy combined with immunization, survival did not exceed two years.25 Nitin Roper et al disclosed that different transcriptional SCLC subtypes could experience clinical benefit to ICIs, as was Notch signaling activation, which might provide the means for more effective application of ICIs in SCLC.26 Chemo-immunotherapy has become the preferred initial treatment for advanced SCLC, but only a small subset of SCLC patients benefits from ICIs, and there is an urgent need for biomarkers with efficient prediction.27

SCLC has long been considered to have higher genomic instability than other types of cancer.28 The inactivation of TP53 and RB1 occurs early in the course of SCLC.29 Inactivation of RB1 allows cells to enter the cell cycle, while TP53 loss can prevent cell cycle arrest and apoptosis. Amplification of Myc family members may enhance cell proliferation, while ASCL1 promotes neuroendocrine fate.30

Furthermore, studies have found that histone modification is highly prevalent in SCLC. Overall, these genetic alterations result in replication stress in SCLC, providing a potential direction for gene intervention therapy. Therefore, the study examined various gene mutations associated with SCLC and the effects of those mutations on the pathogenesis of clinical events and their prognosis. In the cbioportal site, we observed whole-genome sequencing of 120 small cell lung cancer (SCLC) tumour samples and matched normal materials.31 The tumour samples in this study were enriched for earlier stages, while tumour samples were all advanced stages in our study. Surgical treatment is considered for less than 5% of early patients limited to the lung parenchyma for SCLC patients. Then, therapeutic options are completely different. The differences in treatment outcomes were not comparable, but there were no significant differences in the frequency of key gene mutation (P53,RB), diagnosis age and sex ratio, indicating that our cohort is representative to some extent.

It is worth mentioning that KaplanMeier curve suggested that SCLC patients with LRP1B or MAP3K13 mutation had shorter PFS in our study. LRP1B (low-density lipoprotein receptor-related protein 1b) is a putative tumor suppressor. Recent evidence suggests that LRP1B might be a genetic marker for immune checkpoint inhibitors (ICI) in multiple types of cancers.32,33 However, nuclear LRP1B, which was released by the intracellular LRP1B domain and transported to the nucleus, increased the invasion activity of breast cancer cells by upregulation of NEAT1.34 Further studies are required to understand the molecular significance of LRP1B in SCLC progression. MAP3K13 (encoding LZK) is an amplified driver gene in head and neck cancer cells and plays a crucial role in maintaining mutant p53 expression.35 Qiang Zhang36 revealed a regulatory pathway that supervised Myc protein stability via MAP3K13-TRIM25-FBXW7 signaling axis, suggesting a potential therapeutic target for cancers that over-express Myc. Considering that MAP3K13 is a targetable oncogenic kinase, its clinical application deserves further investigation in SCLC.

Researchers found that MSH6 mutations have a better prognosis compared to SPEN mutations. DNA mismatch repair genes (MMR) function in maintaining genomic stability. The dysfunction of MMR genes could lead to accumulation during the repair process of DNA and lead to gene instability and overexpression of cancer-related genes, causing tumor initiation and progression.37 Nine MMR genes related to human mismatch repair have been isolated from human bacteria. MMR is a bacterial MUTS homologue and mainly forms a mismatch complex with MSH2 (MSH2-MSH6) to play a role in mismatch repair.38,39

SPEN family transcriptional repressor (SPEN), also known as SMART/HDAC1-related repressor protein, can regulate transcription and is essential for X chromosome inactivation.40,41 Multiple studies have demonstrated that SPEN can perform different functions in tumorigenesis. SPEN mutation alters a protein complex that represses the transcription of chronic lymphocytic leukemia NOTCH1 target genes.42 SPEN induces miR-4652-3p expression by activating PI3K/AKT/c-JUN signaling to target HIPK2.43 High levels of SPEN RNA are associated with early metastasis in two independent cohorts of 77 (HR 2.25, P = 0.03) and 170 (HR = 2.23, P = 0.004) patients with ER-negative breast cancer.44 In contrast, SPEN is a tumor-suppressor gene that may be clinically useful as a predictive biomarker of tamoxifen response in ER-positive breast cancers.45 In colon cancer, it acts as an oncogene for its pathogenesis, since it positively regulates Wnt signaling.46 However, the molecular mechanism of SPEN in SCLC remains unknown. In our cohort, the OS of SCLC patients with SPEN mutation decreased significantly, indicating that SPEN could be used as a prognostic biomarker.

PI3K/Akt-mediated pathways have been implicated in many tumors. PIK3CA is a P110 catalytic subunit of phosphatidylinositol-3 kinases (PI3Ks), which encodes the PIK3CA protein, namely PI3KP110A.47 PIK3CA plays a role in multiple signaling pathways and controls cellular functions.48 Among them, PIK3CA encoding PI3KP110A is the only oncogenic gene with somatic mutation among the members of the PI3K family found at present. About 4/5 mutations of PIK3CA occur in two hot spots, the helix region (Exon 9) and the kinase region (Exon 20).49 PIK3CA has been identified as an oncogene based on its function and genetics. In tumor cells, the pathogenic mutation of PIK3CA causes abnormal encoding of the p110 subunit that leads to continuous activation of PI3K enzyme. Furthermore, it can activate the downstream Akt, causing independent cell proliferation and enhancing the ability of cells to metastasize.50,51 A series of PIKK3CA mutations have been reported in various cancer lines, including SCLC (3.44.3%), colorectal cancer (3040%), ovarian cancer, thyroid,52,53 cancer,54 gastric cancer, and breast cancer (740%).55 This gene has also been targeted in previous studies of SCLC. Triciribine, a small-molecule Akt inhibitor, was found to act as a pathway inhibitor and was more sensitive to SCLC types with PIK3CA mutations.56 In this study, three samples had PIK3CA mutations, and all of them had bone metastases, resulting in a poor prognosis for the patients. Further studies are needed to understand how this gene could improve the treatment of patients with SCLC.

FAT1 is a member of the cadherin superfamily, which encodes procadherin and is frequently mutated in human cancers, especially squamous cell carcinoma.57,58 Similarly, our results also showed that nonsense mutations of FAT1 are common and can cause loss of gene function. Previous studies have linked FAT1 mutations to poor outcomes in cancer patients. Recurrent somatic mutation of FAT1 in multiple human cancers could result in aberrant Wnt signaling activation, thus promoting the tumor progression.59,60 Studies have demonstrated that FAT1 can encode a protein that binds to -catenin and antagonizes -catenin to enter cells to target and activate Wnt that can inhibit cell proliferation and tumor growth.61 The experiments on constructed mouse models of skin squamous cell carcinoma and lung cancer found that loss of FAT1 can inhibit adhesion and promote epithelial to mesenchymal cell transformation (EMT) and thus promote tumor genesis, development and metastasis.62 From an independent International Cancer Genome Consortium dataset, FAT1 mutation in oral cancer co-occurred with the top mutated genes TP53 and CASP8. Poor overall survival or progression-free survival was observed in patients with FAT1 mutation or altered HER3_pY1289, IRS1, or CAVEOLIN. Pathway analysis revealed dominant ERBB/neuregulin pathways mediated by FAT1 mutations in HNSCC.63 FAT1 plays various roles in different types of cancer and can be used as an oncogene or a tumor suppressor gene. Studies have confirmed that the expression of FAT1 in liver cancer is higher and acts as a tumor protector than in nontumor liver tissue.64,65 Our results show that patients with FAT1 mutation were more prone to liver metastasis, an alternative therapeutic target for SCLC patients. Farago et al reported that combining olaparib and temozolomide in relapsed SCLC could significantly improve the prognosis of SCLC patients.66 After that, they identified a molecular signature predictive of the response to this regimen. Olaparib is PARP inhibitor and has been proved to be effective for BRCA-mutated metastatic breast cancer and ovarian cancer.67,68 We found BRCA2 mutant in our SCLC cohort, which might suggest better sensitivity to olaparib.

Next-generation sequencing demonstrates that the genetic landscape of SCLC is different from that of adenocarcinoma and squamous cell carcinoma. Part mutant genes are linked to clinical factors to some extent. Mutation status of LRP1B, MAP3K13, MSH6 and SPEN has prognostic significance, which might be potential therapeutic targets. We found possible genes and related signaling pathways that affect metastasis. Oncologists might acquire important information to assist in therapeutic options and prognosis evaluation, and SCLC patients might benefit from NGS in clinical practice, and the underlying mechanism deserves further investigation.

We are grateful to all peer reviewers and editors for their opinions and suggestions.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

This work was supported by grants from Henan Cancer Hospital Doctors Initiation Foundation (Grant No. 310103010210962) and Medical Science and Technology Research Program of Henan Province (Grant No. LHGJ20190636). Natural Science Foundation of Henan Province (Grant No.222300420353).

The authors declare that they have no conflicts of interest in this work.

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Genetic Alteration and Their Significance on Clinical Events | CMAR - Dove Medical Press

In PLOS Genetics, researchers from Texas A&M University and Colorado State University describe host genetics-related survival differences in mouse models of infection with the Salmonella enterica serovar Typhimurium, which causes typhoid fever. Using nearly three dozen genetically distinct mouse strains from the Collaborative Cross collection, the team tracked clinical features and outcomes in the days following oral infection with S. Typhimurium. Along with lower-than-usual body temperatures and activity levels prior to infection, the authors linked survival to new and known risk loci on chromosomes 1, 2, 4, and 7. "We identified a broad range of outcomes across these different mice, including a group of mice susceptible to lethal infection and a group that survived our [seven] day study," the authors write, noting that the study "defines the utility of exploring how host genetic diversity influences infection outcomes with bacterial pathogens."

For another paper in PLOS Genetics, a team from the Huazhong University of Science and Technology and other centers in China and the US present evidence of altered RNA splicing in lung tissues from nine fatal COVID-19 cases from the initial Wuhan wave and 10 control samples. With a combination of proteomic profiling and transcriptome sequencing, the researchers saw transcript splicing shifts and alternative transcript usage, particularly when it came to genes related to blood coagulation, immune function, and antiviral activity. "[T]he dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity," they report, noting that "SARS-CoV-2 proteins directly engage host spliceosome to dysregulate essential steps of mature mRNA production and result in widespread dysregulation of cellular function."

Investigators reporting in PLOS One describe apparent genetic ties between intracranial aneurysm and acute ischemic stroke in individuals from Korea, demonstrating with the development of a polygenic risk score (PRS) linked to the risk of both conditions. The team settled on a PRS model for predicting intracranial aneurysm by analyzing weighted PRS models established using data from a prior genome-wide association study that included more than 470 intracranial aneurysm or acute ischemic stroke cases, and nearly 300 unaffected controls, subsequently linking the resulting PRS to elevated risk of acute ischemic stroke as well. Based on these and other results, the authors suggest that intracranial aneurysm and acute ischemic stroke "may have a shared genetic architecture and should be studied further to generate a precision medicine model for use in personalized diagnosis and treatment.

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PLOS Papers on Typhoid Fever Host Genetics, COVID-19-Related RNA Splicing, More - GenomeWeb

Market Situation

In the course of the study, the researchers took a look at the use of COVID-19 on company operators, allies, and disruptors. Because of the wide availability of locks in different areas and nations, the results may vary significantly across sections and regions. Research studies both short- and long-term industrial impacts, and also assists in helping governments formulate short- and long-term business strategies for each specific geographic area.

The Global Animal Genetics Market analysis report is the outcome of incessant efforts guided by knowledgeable forecasters, innovative analysts and brilliant researchers. With the specific and state-of-the-art information provided in this report, businesses can get idea about the types of consumers, consumers demands and preferences, their perspectives about the product, their buying intentions, their response to particular product, and their varying tastes about the specific product which is already present in the market. By providing an absolute overview of the market, Animal Genetics Market report covers various aspects of market analysis, product definition, market segmentation, key developments, and the existing vendor landscape.

In addition to investigating external factors, which are anticipated to have a good or unfavorable effect on the company, an analyst evaluates internal elements to give decision-makers a solid long-term prognosis for the industry. An analysis may examine market segments and forecast the size of the worldwide market. The findings reveal that investment prospects gain greater insight when conducting a competitive analysis, developing their product profile, evaluating prices, gauging a companys financial position, laying out a long-term development strategy, and discussing their footprint on the global market of the Animal Genetics.

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Animal Genetics Market Report Scope

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The growth of this business is very new, and as a result, it exacerbates many of the risks. This article details many of the issues faced by the industry, and I have included it here as a reference. While we generally focus on the law and smart city regulations, our specific interests are Animal Genetics. SWOT Review and Market Strategies have an effect on prominent industry players. According to the study, the report looks at leaders in the sector, including information on companies, products and services, and information given over the past four years, which is a significant shift over the previous five years.

Players Stance

The study provides a list of the top Animal Genetics industry players whose SWOT analysis and market strategies were impacted by the research. Additionally, the research focuses on knowAnimal Geneticsge leaders, such as company profiles, goods, and services that have produced financial data during the last four years, a substantial change from the prior five years:

Animal Genetics Market Segmentations:

Global Animal Genetics Market: Type Segment Analysis

Global Animal Genetics Market: Application Segment Analysis

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Global Animal Genetics Market Regional Outlook:

This market segmentation research is designed to provide complete market segmentation data in the following areas: Solution, Business, End-User, and Geography. Global demand for Animal Genetics is expected to see significant increase over the projected period. This study provides important market position statistics to industry leaders, which gives them information on current industry trends and future prospects. The Rowelto Associates uses business techniques and objective consumer knowAnimal Geneticsge to provide favorable outcomes. Projections and forecasts, as well as unfettered technical evaluations by sector, are possible if you do study. One data-driven research and quality recommendations for CXOs, CEOs, government officials, and investors is all wrapped up in this approach. With more insights, consumers will have greater motivation to solve issues.

The report provides insights on the following pointers:

1. Market Penetration: Provides comprehensive information on the market offered by the key players2. Market Development: Provides in-depth information about lucrative emerging markets and analyze penetration across mature segments of the markets3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, certification, regulatory approvals, patent landscape, and manufacturing capabilities of the leading players5. Product Development & Innovation: Provides intelligent insights on future technologies, R&D activities, and breakthrough product developments

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Animal Genetics Market Incredible Possibilities, Growth With Industry Study, Detailed Analysis And Forecast To 2029 Blackswan Real Estate - Blackswan...

Universit de Lille, INSERM, CHU Lille, Institut Pasteur Lille, U1167-RID-AGE, Facteurs de risque et dterminants molculaires des maladies lies au vieillissement, Lille, France

Cline Bellenguez,Benjamin Grenier-Boley,Vincent Damotte,Marcos R. Costa,Julien Chapuis,R. Pineda-Snchez,Nathalie Fievet,Hieab Adams,Philippe Amouyel&Jean-Charles Lambert

Complex Genetics of Alzheimers Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium

Fahri Kkali,Christine Van Broeckhoven,Jasper Van Dongen&Kristel Sleegers

Laboratory of Neurogenetics, Institute Born - Bunge, Antwerp, Belgium

Fahri Kkali,Christine Van Broeckhoven,Jasper Van Dongen&Kristel Sleegers

Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

Fahri Kkali,Jasper Van Dongen&Kristel Sleegers

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands

Iris E. Jansen,Sven J. van der Lee,Henne Holstege,Marc Hulsman,Yolande A. L. Pijnenburg,Philip Scheltens,Niccolo Tes&Wiesje M. van der Flier

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije University, Amsterdam, the Netherlands

Iris E. Jansen,Danielle Posthuma&Tim Lu

Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany

Luca Kleineidam,Victor Andrade,Michael T. Heneka,Wolfgang Maier,Anja Schneider,Michael Wagner,Kayenat Parveen,Frank Jessen&Alfredo Ramirez

Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University of Cologne, Medical Faculty, Cologne, Germany

Luca Kleineidam,Rafael Campos-Martin,Victor Andrade,Maria Carolina Dalmasso,Klaus Fliebach&Alfredo Ramirez

German Center for Neurodegenerative Diseases (DZNE Bonn), Bonn, Germany

Luca Kleineidam,Klaus Fliebach,Michael T. Heneka,Wolfgang Maier,Matthias Schmid,Anja Schneider,Annika Spottke,Michael Wagner,Henning Boecker,Andr Lacour,Christine Herold,Tim Becker,Ying Wu,Yanbing Wang,Frank Jessen&Alfredo Ramirez

Research Center and Memory Clinic Fundaci ACE, Institut Catal de Neurocincies Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain

Sonia Moreno-Grau,Itziar de Rojas,Pablo Garcia-Gonzalez,Carla Abdelnour,Emilio Alarcn-Martn,Montserrat Alegret,Merc Boada,Miguel Calero,Ana Espinosa,Pablo Garca-Gonzlez,Isabel Hernndez,Marta Marqui,Laura Montrreal,Adelina Orellana,Gemma Ortega,Alba Prez-Cordn,Raquel Puerta,Natalia Roberto,Maite Rosende-Roca,ngela Sanabria,Oscar Sotolongo-Grau,Juan Pablo Tartan,Llus Trraga,Sergi Valero,Ana Maulen,Ana Pancho,Anna Gailhajenet,Asuncin Lafuente,Elvira Martn,Esther Pelej,Liliana Vargas,Mar Buendia,Marina Guitart,Mariona Moreno,Marta Ibarria,Nuria Aguilera,Pilar Caabate,Silvia Preckler,Susana Diego,Nuria Aguilera,Amanda Cano,Pilar Caabate,Ral Nuez-Llaves,Cludia Oliv,Ester Pelej&Agustn Ruiz

CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain

Sonia Moreno-Grau,Itziar de Rojas,Pablo Garcia-Gonzalez,Carla Abdelnour,Daniel Alcolea,Montserrat Alegret,Rafael Blesa,Merc Boada,Dolores Buiza-Rueda,Laura Cervera-Carles,Ana Espinosa,Juan Fortea,Mara J. Bullido,Ana Frank-Garca,Jose Maria Garca-Alberca,Isabel Hernndez,Carmen Lage,Alberto Lle,Adolfo Lopez de Munain,Marta Marqui,Angel Martn Montes,Miguel Medina,Pablo Mir,Fermin Moreno,Adelina Orellana,Gemma Ortega,Jordi Prez-Tur,Alberto Rbano,Eloy Rodriguez-Rodriguez,Maite Rosende-Roca,ngela Sanabria,Pascual Snchez Juan,Llus Trraga,Sergi Valero,Miren Zulaica,Ad Adarmes-Gmez,D. Macias-Garca,F. Carrillo,Isabel Sastre Merln,L. Garrote-Espina,M. Carrion-Claro,Ma Labrador,Mt Perin,P. Gmez-Garre,R. Escuela,R. Vigo-Ortega,S. Jess,Nuria Aguilera,Pilar Caabate,Astrid D. Adarmes-Gmez,Ftima Carrillo,Mario Carrin-Claro,Roco Escuela,Lorena Garrote-Espina,Pilar Gmez-Garre,Silvia Jess,Miguel Angel Labrador Espinosa,Sara Lpez-Garca,Daniel Macias-Garca,Mara Teresa Perin-Tocino,Roco Pineda-Snchez,Isabel Sastre,Rosario Vigo-Ortega,Jordi Clarimon&Agustn Ruiz

Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands

Najaf Amin,Amber Yaqub,Ivana Prokic,Shahzad Ahmad,Hata Comic,Tavia Evans,Maria Knol,William Kremen,Gena Roshchupkin,Dina Vojinovic,Mohsen Ghanbari,M. Arfan Ikram&Cornelia M. van Duijn

Nuffield Department of Population Health, Oxford University, Oxford, UK

Najaf Amin&Cornelia M. van Duijn

Department of Biostatistics, Epidemiology, and Informatics, Penn Neurodegeneration Genomics Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Adam C. Naj,Jin Sha,Alessandra Chesi,Beth A. Dombroski,Jacob Haut,Pavel P. Kuksa,Chien-Yueh Lee,Edward B. Lee,Yuk Yee Leung,Mingyao Li,John Malamon,Liming Qu,John Q. Trojanowski,Otto Valladares&Vivianna M. Van Deerlin

Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Adam C. Naj,Valentina Escott-Price,Pavel P. Kuksa,Chien-Yueh Lee,Otto Valladares,Li-San Wang,Yi Zhao&Gerard D. Schellenberg

MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK

Peter A. Holmans,Catherine Bresner,Janet Harwood,Lauren Luckcuck,Rachel Marshall,Amy Williams,Charlene Thomas,Chloe Davies,William Nash,Kimberley Dowzell,Atahualpa Castillo Morales,Mateus Bernardo-Harrington,Julie Williams&Rebecca Sims

CEA, Centre National de Recherche en Gnomique Humaine, Universit Paris-Saclay, Evry, France

Anne Boland,Cline Besse,Delphine Daian,Bertrand Fin,Robert Olaso&Jean-Franois Deleuze

Section Genomics of Neurodegenerative Diseases and Aging, Department of Human Genetics Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands

Sven J. van der Lee,Henne Holstege,Marc Hulsman,Yiyi Ma&Niccolo Tes

Brain Institute, Federal University of Rio Grande do Norte, Natal, Brazil

Marcos R. Costa&Mikko Hiltunen

Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland

Teemu Kuulasmaa,Alexa Beiser,Anita DeStefano,Kathryn L. Lunetta,Gina Peloso,Ruiqi Wang,Neil W. Kowall,Ann C. McKee,Jesse Mez,Robert A. Stern&Lindsay A. Farrer

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

Qiong Yang,Anita DeStefano,Lena Kilander,Malin Lwemark,Claudia L. Satizabal,Ruiqi Wang,Adrienne L. Cupples,Jose Dupuis,Shuo Li,Xuan Liu&Sudha Seshadri

Framingham Heart Study, Framingham, MA, USA

Qiong Yang,Oscar Lopez&Bruce M. Psaty

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA

Joshua C. Bis&Alison E. Fohner

LACDR, Leiden, the Netherlands

Shahzad Ahmad

Department of Public Health and Carins Sciences/Geriatrics, Uppsala University, Uppsala, Sweden

Vilmantas Giedraitis&Martin Ingelsson

Centre of Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway

Dag Aarsland

Institute of Psychiatry, Psychology & Neuroscience, London, UK

Dag Aarsland

Department of Surgery, Biochemistry and Molecular Biology, School of Medicine, University of Mlaga, Mlaga, Spain

Emilio Alarcn-Martn

Department of Neurology, II B Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autnoma de Barcelona, Barcelona, Spain

Daniel Alcolea,Rafael Blesa,Laura Cervera-Carles,Juan Fortea,Alberto Lle,Martin Rossor&Jordi Clarimon

Fundaci Docncia i Recerca MtuaTerrassa and Movement Disorders Unit, Department of Neurology, University Hospital MtuaTerrassa, Terrassa, Spain

Ignacio Alvarez,Mnica Diez-Fairen&Pau Pastor

Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Spain

Ignacio Alvarez,Mnica Diez-Fairen&Pau Pastor

Laboratorio de Gentica, Hospital Universitario Central de Asturias, Oviedo, Spain

Victoria lvarez&Irene Rosas Allende

Servicio de Neurologa, Hospital Universitario Central de Asturias- Oviedo and Instituto de Investigacin Biosanitaria del Principado de Asturias, Oviedo, Spain

Victoria lvarez,Carmen Martnez Rodrguez,Manuel Menndez-Gonzlez&Irene Rosas Allende

Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

Nicola J. Armstrong,Henry Brodaty,Anbupalam Thalamuthu,Perminder Sachdev&Karen Mather

First Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

Anthoula Tsolaki,Tegos Thomas,Anna Anastasiou&Magda Tsolaki

Alzheimer Hellas, Thessaloniki, Greece

Anthoula Tsolaki,Tegos Thomas&Magda Tsolaki

Unidad de Demencias, Hospital Clnico Universitario Virgen de la Arrixaca, Murcia, Spain

Carmen Antnez,Martirio Antequera,Agustina Legaz,Juan Marn-Muoz,Begoa Martnez,Victoriana Martnez,Maria Pilar Vicente&Liliana Vivancos

School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy

Ildebrando Appollonio,Elisa Conti,Lucio Tremolizzo,Carlo Ferrarese,Simona Andreoni,Gessica Sala&Chiara Paola Zoia

Neurology Unit, San Gerardo Hospital, Monza, Italy

Ildebrando Appollonio,Lucio Tremolizzo&Carlo Ferrarese

Fondazione IRCCS CaGranda, Ospedale Policlinico, Milan, Italy

Marina Arcaro,Daniela Galimberti&Elio Scarpini

Department of Laboratory Diagnostics, III Laboratory of Analysis, Brescia Hospital, Brescia, Italy

Silvana Archetti

Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain

Alfonso Arias Pastor,Raquel Huerto Vilas&Gerard Piol-Ripoll

Institut de Recerca Biomedica de Lleida (IRBLLeida), Lleida, Spain

Alfonso Arias Pastor,Raquel Huerto Vilas&Gerard Piol-Ripoll

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

Beatrice Arosio

Geriatic Unit, Fondazione C Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy

Beatrice Arosio,Simona Ciccone,Paolo Dionigi Rossi&Evelyn Ferri

NORMENT Centre, University of Oslo, Oslo, Norway

Lavinia Athanasiu,Srdjan Djurovic,Alexey A. Shadrin,Shahram Bahrami&Ole A. Andreassen

EA 4468, Universit de Paris, APHP, Hpital Broca, Paris, France

Henri Bailly,Emmanuelle Duron,Olivier Hanon&Jean-Sbastien Vidal

Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy

Nerisa Banaj,Gianfranco Spalletta,Francesca Assogna,Fabrizio Piras,Federica Piras,Valentina Ciullo,Jacob Shofany&Yi Zhao

Servei de Neurologia, Hospital Universitari i Politcnic La Fe, Valencia, Spain

Miquel Baquero&Juan Andrs Burguera

Taub Institute on Alzheimers Disease and the Aging Brain, Department of Neurology, Columbia University, New York, NY, USA

Sandra Barral,Richard Mayeux,Nikolaos Scarmeas,Giuseppe Tosto,Badri N. Vardarajan,Sandra Barral,Lawrence S. Honig,Scott Small,Jean-Paul Vonsattel&Jennifer Williamson

See original here:
New insights into the genetic etiology of Alzheimer's disease and related dementias - Nature.com

SALT LAKE CITY Theres a 13% chance for any woman to develop breast cancer in the course of their lifetime. But for 24-year-old twins, Emma and Gabriella Friel. theres a much higher chance. An 80% change.

The sisters, from Utah, live together, hike together, snowboard together, travel together and so much more. And recently, they underwent double mastectomies together on the same day, at the same hospital.

In early 2021, Emma, who works in the genetics field, set out to satisfy a nagging worry she had about her genealogy and genetics: Was her family history of breast cancer a sign that she had inherited a gene mutation that put her at a very high risk of developing the disease?

This BRCA gene runs in our family, said Emma. Our cousin had it and her mom, so our aunt had it. It was very off-handed. I got tested, I didnt think anything about it, I figured I would be negative and then it turned out I was positive.

Emmas test result foreshadowed Gabriellas.

I was hoping, by some chance, that I wouldnt have it, said Gabriella. I dont know, by the grace of God or something, but I assumed I did.

The results were back within a month. They both had the BRCA1 gene.And then they had a decision to make.

So, theres a 13% chance for women to get breast cancer in their life. For the Friel sisters, its six times that.

There is about an 85% chance of us developing breast cancer by the time we turn 70, 75, explained Emma. Its not super scientific where they can see, like this is your percentage by the age of 30. And this is your percentage by the age of 50. Its very broad. Theyre doing more research to try and pinpoint it. But science isnt there yet.

Emma decide she would undergo a double mastectomy to significantly cut her odds for developing the disease. Gabriella looked into other options.

Another option is I could get tested every six months for the rest of my life until someday I get breast cancer, said Gabriella. I wasnt keen on that option. It just seemed like a lot of anxiety, and a lot of time.

In February 2022, both admitted themselves to the same hospital, on the same day, to undergo double mastectomies.

Emma and Gabriellas mother, Sandra Garofalo was the first person Emma called after she got her test results.

I just, I immediately felt guilty, said Garofalo. I thought I should have tested myself long ago, like I, I just made a lot of excuses of why not to get tested, you know. I had lost my cousin. And I knew that she was positive. But you know, our parents are half-siblings. And they had breast cancer on the side of the family that was not blood-related to me. So I just always kind of thought, Oh, it must have come from that side of the family. I put it out of my head for a long time.

The irony is, that Garofalo is a nurse practitioner who works with cancer patients.

Heres Emma, the first one positive, and I immediately felt like this should not be on her, I should have done this first, she said. I want them to make the right decision, but I know that it needs to be theirs, and not mine.

She says she would be there to emotionally support them, but not make the decision for them.

Of course, I didnt want them to get it yet, Garofalo said. Theyre really active, and theyre having so much fun. I dont want to interrupt their lives with this mess and thinking about cancer. As I was struggling over that, I met a new patient, literally a week, after all of this kind of hit. And this girl walks in. Shes one year older than my twins. Shes this really dynamic young woman. And shes like the girl she likes to rock climb and snowboard and adventure and do all this stuff. And shes BRACA-1 positive, and she has triple-negative breast cancer, which is traditionally a harder cancer to treat and harder to cure. Ive been going through wrestling with this, that it was this way of saying this is what you need to do. Theyre doing the right thing. Theyre not too young to get surgery.

All the while, Garofalo got tested herself. She was positive for the gene, too.

So while her girls were weighing their options, Garofalo got her double mastectomy in the fall of 2021.

The BRCA-1 and BRCA-2 are genes that women normally have two copies of that help protect them from cancer. If one of the genes we inherit is defective, it puts the bodys ability to fight cancer at a disadvantage.

They are more at risk for getting breast, ovarian cancer, sometimes pancreas, melanoma, and men, of course, are more at risk for getting prostate cancer, said Huntsman Cancer Institutes Dr. Sarah Colonna.

Colonna wasnt involved in the Friel sisters diagnosis.

She recommends speaking to a genetic counselor before making the decision to test for gene mutations and says there are a couple of options: One is an FDA-approved at-home saliva test, and the other is to get tested at your doctors office.

Costs used to be several thousand dollars, its come down. Now its like a couple of hundred dollars.

She warns federal law makes it illegal for health insurance companies to base coverage on a persons DNA but things differ when it comes to life and disability insurance.

And though Colonna urges people to consider the insurance implication before testing themselves, she says that by undergoing double mastectomies Emma and Gabriella significantly dropped their risk of cancer.

Lets say Gabriellas risk was 70%, said. Colonna. A risk-reducing mastectomy would take it from 70% to 7%.

The FDA has approved an at-home test kit, and the genetic testing website 23andMe markets a saliva test, which costs about $200.

We test for the three mutations on the BRCA1 and BRCA2 genes that are some of the most common, the most well-studied and convey the largest risk. We do not test for all possible variants in the BRCA1 and BRCA2 genes, as more than 1,000 variants in these genes are known to increase cancer risk, a spokesperson responded to KSL NewsRadios inquiry.

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General Conference: Two sisters used genealogy, genetics to find their risk of breast cancer - KSL NewsRadio