A5044134713- BRCA gene mutations in cancer
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Nutrition, Genetics, and Disease
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- Renal cell carcinoma treatment
- Health Systems, Economic Evaluations, Quality of Life
- Prostate Cancer Treatment and Research
- Fetal and Pediatric Neurological Disorders
- Tuberous Sclerosis Complex Research
- Pancreatic and Hepatic Oncology Research
- Genetics, Bioinformatics, and Biomedical Research
- PARP inhibition in cancer therapy
- Genetic and Kidney Cyst Diseases
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Statistical Methods in Clinical Trials
- Genomics and Chromatin Dynamics
- Autism Spectrum Disorder Research
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
Autism & Developmental Medicine Institute
2021-2025
Geisinger Health System
2024
Mayo Clinic
2017-2023
Mayo Clinic in Arizona
2014-2023
Kingston Health Sciences Centre
2023
Queen's University
2023
Mayo Clinic in Florida
2017-2022
University of Maryland, Baltimore
2009-2022
WinnMed
2017-2022
Ambry Genetics (United States)
2018
Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance germline other genes from multigene hereditary cancer testing panels is not well defined.To determine risks associated with predisposition genes.A study population 65 057 patients receiving genetic panels. Associations between non-BRCA1 non-BRCA2 were estimated a case-control analysis Exome Aggregation Consortium reference controls. The women underwent March 15,...
Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose and the risks of associated with mutations in these genes are not well defined.To determine whether inherited germline predisposition increased cancer.Case-control analysis identify genes; longitudinal patients for prognosis. The study included 3030 adults diagnosed as having enrolled a Mayo Clinic registry between October 12, 2000, March 31, 2016, last follow-up on June 22, 2017....
Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those triple-negative (estrogen receptor–negative, progesterone human epidermal growth factor receptor–negative) (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim this study was to define the panel associated TNBC. Multigene 21 in 8753 TNBC patients performed by a clinical laboratory, and 17 2148...
We previously showed that the 44-kDa serine/threonine kinase Pim-1 (Pim-1L) can protect prostate cancer cells from apoptosis induced by chemotherapeutic drugs (Xie, Y., Xu, K., Dai, B., Guo, Z., Jiang, T., Chen, H., and Qiu, Y. (2006) Oncogene 25, 70–78). To further explore mechanisms of Pim-1L-mediated resistance to in cells, we employed a yeast two-hybrid screening identify cellular proteins were associated with Pim-1L, found ABC transporter BCRP/ABCG2 as one potential interacting partners...
Significance The major portion of hereditary breast cancer still remains unexplained, and many susceptibility loci are yet to be found. Exome sequencing 24 high-risk familial BRCA1/2 -negative patients further genotyping a large sample set breast/ovarian cases controls was used discover previously unidentified alleles genes. A significant association FANCM nonsense mutation with cancer, especially triple-negative identifies as gene. Identification such risk is expected improve assessment for...
Genetic predisposition to male breast cancer (MBC) is not well understood. The aim of this study was better define the genes contributing MBC and utility germline multi-gene panel testing (MGPT) for explaining etiology MBCs. Clinical histories molecular results were retrospectively reviewed 715 patients who underwent MGPT from March 2012 June 2016. detection rate 18.1% tested variants in 16 susceptibility with no prior BRCA1/2 testing. BRCA2 CHEK2 most frequently mutated (11.0 4.1% testing,...
Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These often treated primary systemic chemotherapy. The aim of this study was to analyze the effects on pathologic complete response (pCR) and disease-free survival (DFS) a cohort TNBC anthracycline taxane–containing chemotherapy, or without bevacizumab. Patients Methods Germline DNA sequenced identify BRCA1 BRCA2 493 from GeparQuinto study. pCR rates were compared mutation, as well In addition,...
Abstract Background The germline cancer predisposition genes associated with increased risk of each clinical subtype breast cancer, defined by estrogen receptor (ER), progesterone (PR), and HER2, are not well defined. Methods A total 54 555 invasive patients 56 480 tumors were subjected to hereditary multigene panel testing. Heterogeneity for across subtypes was assessed comparing mutation frequencies gene among tumor association studies between reference controls. Results Mutations in 15...
Progression from the androgen-sensitive to androgen-insensitive (or castration-resistant) stage is major obstacle for sustained effectiveness of hormonal therapy prostate cancer. The androgen receptor (AR) and its splice variants play important roles in regulating transcription program essential castration resistance. Here, we report identification a novel AR variant, designated as AR8, which up-regulated castration-resistant cancer cells. AR8 structurally different other known because it...
Breast cancer risks conferred by many germline missense variants in the
To improve methods for predicting the impact of missense variants uncertain significance (VUS) in BRCA1 and BRCA2 on protein function.Functional data 248 207 from assays with established high sensitivity specificity damaging were used to recalibrate 40 silico algorithms activity. Additional random forest (RF) naïve voting method (NVM) metapredictors both developed increase predictive accuracy.Optimized thresholds prediction models significantly improved accuracy predicted functional effects...
The relevance of inherited pathogenic mutations in cancer predisposition genes pancreatic is not well understood. We aimed to assess the characteristics patients with referred for hereditary genetic testing and estimate risk associated panel-based this high-risk population.
Genetic testing of individuals often results in identification genomic variants unknown significance (VUS). Multiple lines evidence are used to help determine the clinical these variants.We analyzed ~138,000 tested by multigene panel (MGPT). We logistic regression predict carrier status based on personal and family history cancer. This was applied 4644 carrying 2383 BRCA1/2 calculate likelihood ratios informing pathogenicity for each. Heterogeneity tests were performed specific classes...
Abstract To evaluate the racial and ethnic differences in prevalence of germline pathogenic variants (PVs) effect race ethnicity on breast cancer (BC) risk among carriers, results multigene testing 77 900 women with BC (non-Hispanic White [NHW] = 57 003; Ashkenazi-Jewish 4798; Black 6722; Hispanic 5194; Asian 4183) were analyzed, frequency PVs each gene compared between patients (cases) race- ethnicity-matched gnomAD reference controls. Compared NHWs, BRCA1 enriched Ashkenazi-Jews Hispanics,...
Penetrance estimates of Birt-Hogg-Dubé syndrome (BHD)-associated cutaneous, pulmonary, and kidney manifestations are based on clinically ascertained families. In a health care system population, we used genetics-first approach to estimate the prevalence pathogenic/likely pathogenic (P/LP) truncating variants in FLCN, which cause BHD, penetrance BHD-related phenotypes.Exomes from 135,990 patient-participants Geisinger's MyCode cohort were assessed for P/LP FLCN variants. phenotypes evaluated...
Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), cardinal feature congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD).
Autism, schizophrenia, and other clinically distinct neurodevelopmental psychiatric disorders (NPDs) have shared genetic etiologies, including single-gene multigenic copy number variants (CNVs). Because rare are primarily investigated in clinical cohorts, population-based estimates of their prevalence penetrance lacking. The authors determined the prevalence, penetrance, NPD risk pathogenic a large health care system population.