A5052818993- BRCA gene mutations in cancer
- Nutrition, Genetics, and Disease
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Genetic Associations and Epidemiology
- Ovarian cancer diagnosis and treatment
- Genomic variations and chromosomal abnormalities
- Breast Cancer Treatment Studies
- Lung Cancer Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Genetic factors in colorectal cancer
- RNA modifications and cancer
- Advanced Breast Cancer Therapies
- Cancer-related molecular mechanisms research
- Radiomics and Machine Learning in Medical Imaging
- Genomics and Rare Diseases
- Cancer Cells and Metastasis
- Cancer Treatment and Pharmacology
- Cancer Risks and Factors
- Pancreatic and Hepatic Oncology Research
- Cardiovascular Health and Risk Factors
- Ferroptosis and cancer prognosis
- Cervical and Thoracic Myelopathy
Myriad Genetics
2015-2024
Myriad (Germany)
2015-2024
NIHR Surgical Reconstruction and Microbiology Research Centre
2020
Queen Elizabeth Hospital
2020
University of Birmingham
2020
Flinders University
2019
Fox Chase Cancer Center
2017
Stanford University
2017
European Institute of Oncology
2013
The University of Texas MD Anderson Cancer Center
2013
Homologous recombination (HR) DNA repair is of clinical relevance in breast cancer. Three DNA-based homologous deficiency (HRD) scores (HRD-loss heterozygosity score (LOH), HRD-telomeric allelic imbalance (TAI), and HRD-large-scale state transition (LST)) have been developed that are highly correlated with defects BRCA1/2, associated response to platinum therapy triple negative ovarian This study examines the frequency BRCA1/2 among different cancer subtypes, ability HRD identify tumors...
Multiple-gene, next-generation sequencing panels are increasingly used to assess hereditary cancer risks of patients with diverse personal and family histories. The magnitude breast ovarian risk associated many clinically tested genes, independent history, remains be quantified.We queried a commercial laboratory database 95,561 women for 25-gene (APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CHEK2, MLH2, MSH2, MSH6, MUTYH, NBN, P14ARF, P16, PALB2, PMS2, PTEN, RAD51C, RAD51D,...
Abstract Pathogenic variants (PVs) in ATM are relatively common, but the scope and magnitude of risk remains uncertain. This study aimed to estimate PV cancer risks independent family history. analysis included patients referred for hereditary testing with a multi-gene panel (N = 627,742). Cancer carriers 4,607) were adjusted history using multivariable logistic regression reported as ORs 95% confidence intervals (CIs). Subanalyses c.7271T>G missense conducted. Moderate-to-high...
<h3>Importance</h3> To date, few studies have examined the extent to which polygenic single-nucleotide variation (SNV) (formerly polymorphism) scores modify risk for carriers of pathogenic variants (PVs) in breast cancer susceptibility genes. In previous reports, modification was reduced for<i>BRCA1</i>and<i>BRCA2</i>PV compared with noncarriers, but limited information is available of<i>CHEK2</i>,<i>ATM</i>, or<i>PALB2</i>PVs. <h3>Objective</h3> examine an 86-SNV score (PRS)...
Abstract Purpose: New prognostic markers to guide treatment decisions in early stage non–small cell lung cancer are necessary improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature cell-cycle progression genes (CCP score) define 5-year risk cancer–related death patients with adenocarcinoma. Experimental Design: A CCP score was calculated from levels 31 proliferation I and II tumor samples two public microarray datasets [Director's Consortium...
The current study evaluated three biomarkers [homologous recombination deficiency (HRD), tumor BRCA1/2 (tBRCA) mutations, and CCNE1 copy-number variation (CNV)] in ovarian tumors from patients enrolled on the SCOTROC4 clinical trial for associations with outcome following carboplatin monotherapy. Ovarian (n = 250), high-grade serous (HGSOC) subgroup analysis 179) were classified as HRD positive (HRD score ≥42 or tBRCA mutation) amplification (CCNE1 CNV >2.4). Seventy-four (30%) positive,...
Women with a family history of breast cancer are frequently referred for hereditary genetic testing, yet < 10% found to have pathogenic variants in known susceptibility genes. Large-scale genotyping studies identified common (primarily single-nucleotide polymorphisms [SNPs]) individually modest risk that, aggregate, account considerable susceptibility. Here, we describe the development and empirical validation an SNP-based polygenic score.
PURPOSE Hereditary cancer genetic testing can inform personalized medical management for individuals at increased risk. However, many variants in predisposition genes are individually rare, and traditional tools may be insufficient to evaluate pathogenicity. This analysis presents data on variant classification reclassification over a 20-year period. PATIENTS AND METHODS is retrospective of > 1.9 million who received hereditary from single clinical laboratory (March 1997 December 2017)....
The IBIS/Tyrer-Cuzick model is used clinically to guide breast cancer screening and prevention, but was developed primarily in non-Hispanic White women. Little known about its long-term performance a racially/ethnically diverse population.The Women's Health Initiative study enrolled postmenopausal women from 1993-1998. Women were included who aged <80 years at enrollment with no prior or mastectomy data required for calculation (weight; height; ages menarche, first birth, menopause;...
PURPOSE PTEN-associated clinical syndromes such as Cowden syndrome (CS) increase cancer risk and have historically been diagnosed based upon phenotypic criteria. Because not all patients clinically with CS PTEN pathogenic variants (PVs), PVs CS, the conferred by calculated from cohorts of diagnoses CS/CS-like phenotypes may be inaccurate. METHODS We assessed a consecutive cohort 727,091 individuals tested for hereditary risk, multigene panel between September 2013 February 2022....
PurposeWe previously described a combined risk score (CRS) that integrates multiple-ancestry polygenic (MA-PRS) with the Tyrer-Cuzick (TC) model to assess breast cancer (BC) risk. Here, we present longitudinal validation of CRS in real-world cohort.MethodsThis study included 130,058 patients referred for hereditary genetic testing and negative germline pathogenic variants BC-associated genes. Data were obtained by linking test results medical claims (median follow-up 12.1 months)....
The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with higher risk cancer-related death after surgical resection early stage (I-II) lung adenocarcinoma in large patient cohort and evaluate the effectiveness combining CCP score pathological for predicting cancer mortality.Formalin-fixed paraffin-embedded tumor samples from 650 diagnosed I II who underwent definitive treatment without adjuvant chemotherapy were...
PURPOSE Screening and prevention decisions for women at increased risk of developing breast cancer depend on genetic clinical factors to estimate select appropriate interventions. Integration polygenic into estimators can improve discrimination. However, correlated effects must be incorporated carefully avoid overestimation risk. MATERIALS AND METHODS A novel Fixed-Stratified method was developed that accounts confounding when adding a new factor an established model. combined score (CRS)...
Abstract Purpose Young age at breast cancer (BC) diagnosis and family history of BC are strongly associated with high prevalence pathogenic variants (PVs) in BRCA1 BRCA2 genes. There is limited evidence for such associations moderate/high penetrance BC-risk genes as ATM , CHEK2 PALB2 . Methods We analyzed multi-gene panel testing results (09/2013–12/2019) women unaffected by any (N = 371,594) those affected 130,151) ascertained suspicion hereditary and/or ovarian cancer. Multivariable...
Polygenic risk scores (PRSs) for breast cancer (BC) stratification have been developed primarily in women of European ancestry. Their application to non-European ancestry has lagged because the lack a formal approach incorporate genetic and ancestry-dependent variant frequencies effect sizes. Here, we propose multiple-ancestry PRS (MA-PRS) that addresses these issues may be useful development equitable PRSs across other cancers common diseases.Women referred hereditary testing were divided...
This study sought to determine the prevalence of PALB2 mutations in a cohort referred for diagnostic testing hereditary breast cancer.Sanger sequencing was used analyze entire coding region and flanking introns anonymized DNA samples from 1479 patients. Samples were stratified into "high-risk" group, 955 individuals predicted have high probability carrying mutation BRCA1 or BRCA2 based on their personal family history, "lower-risk" group consisting 524 patients with cancer, but fewer risk...
PURPOSE Breast cancer risks for CHEK2 and ATM pathogenic variant (PV) carriers are modified by an 86-single nucleotide polymorphism polygenic risk score (PRS) individual clinical factors. Here, we describe comprehensive prediction models women of European ancestry combining PV status, PRS, variables. MATERIALS AND METHODS This study included deidentified records from 358,095 who received testing with a multigene panel (September 2013 to November 2019). Model development (n = 4,286), 2,666),...
Abstract Purpose: The EndoPredict prognostic assay is validated to predict distant recurrence and response chemotherapy primarily in post-menopausal women with estrogen receptor–positive (ER+), HER2− breast cancer. This study evaluated the performance of pre-menopausal women. Experimental Design: Tumor samples from 385 ER+, primary cancer (pT1-3, pN0-1) who did not receive addition endocrine therapy were tested produce a 12-gene EP molecular score an integrated EPclin that includes...
1579 Background: Women who are unaffected with cancer but have a significant family history of breast (BC) frequently referred for hereditary testing multi-gene panels; however, < 10% test positive clinically actionable mutations. Large-scale genotyping studies identified common variants (primarily single-nucleotide polymorphisms) that individually confer modest BC risk, together may explain the genetic susceptibility in many women without monogenic Here, we describe development and...
Lynch syndrome is a hereditary cancer associated with high risks of colorectal and endometrial that caused by pathogenic variants in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM). Accurate classification identified these as or benign enables informed medical management decisions. Previously, we developed clinical History Weighting Algorithm (HWA) for uncertain significance (VUSs) BRCA1 BRCA2. The BRCA1/2 HWA based on premise will be more often individuals strong personal and/or...