Steven N. Hart
A5085507659- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Health Systems, Economic Evaluations, Quality of Life
- Genetic factors in colorectal cancer
- Genomics and Rare Diseases
- Pancreatic and Hepatic Oncology Research
- Nutrition, Genetics, and Disease
- DNA Repair Mechanisms
- Genetic Associations and Epidemiology
- AI in cancer detection
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- Advanced Causal Inference Techniques
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Prostate Cancer Treatment and Research
- Genomic variations and chromosomal abnormalities
- Pharmacogenetics and Drug Metabolism
- Multiple and Secondary Primary Cancers
- Science, Research, and Medicine
- Radiomics and Machine Learning in Medical Imaging
- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
Mayo Clinic in Arizona
2016-2025
Mayo Clinic in Florida
2015-2024
Mayo Clinic
2013-2024
WinnMed
2013-2024
University College London
2024
Breast Cancer Research Foundation
2022
Massachusetts General Hospital
2021
Harvard University
2021
American Military Academy
2020
United States Military Academy
2020
Population-based estimates of the risk breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for assessment and management women inherited variants.
Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing patients. We assessed frequency mutations 17 predisposition genes, including BRCA1 and BRCA2, a large cohort patients with triple-negative (TNBC) unselected family history or ovarian determine utility those TNBC. Patients Methods TNBC (N = 1,824) were recruited through 12 studies, was sequenced identify mutations. Results Deleterious identified 14.6%...
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....
Given the high technical reproducibility and orders of magnitude greater resolution than microarrays, next-generation sequencing mRNA (RNA-Seq) is quickly becoming de facto standard for measuring levels gene expression in biological experiments. Two important questions must be taken into consideration when designing a particular experiment, namely, 1) how deep does one need to sequence? and, 2) many replicates are necessary observe significant change expression?Based on distributions from...
HepaRG cells, derived from a female hepatocarcinoma patient, are capable of differentiating into biliary epithelial cells and hepatocytes. More importantly, differentiated able to maintain activities many xenobiotic-metabolizing enzymes, expression the metabolizing enzyme genes can be induced by xenobiotics. The ability these express induce enzymes is in stark contrast frequently used HepG2 cells. previous studies have mainly focused on set selected genes; therefore, it significant interest...
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...
As reliable, efficient genome sequencing becomes ubiquitous, the need for similarly reliable and variant calling increasingly important. The Genome Analysis Toolkit (GATK), maintained by Broad Institute, is currently widely accepted standard software. However, alternative solutions may provide faster without sacrificing accuracy. One such Sentieon DNASeq, a toolkit analogous to GATK but built on highly optimized backend. We conducted an independent evaluation of DNASeq single-sample pipeline...
PurposeDespite the rapid uptake of multigene panel testing (MGPT) for hereditary cancer predisposition, there is limited guidance surrounding indications and genes to include.MethodsTo inform clinical approach MGPT, we comprehensively evaluated 32 predisposition by assessing phenotype-specific pathogenic variant (PV) frequencies, risk associations, performance genetic criteria in a cohort 165,000 patients referred MGPT.ResultsWe identified extensive heterogeneity types commonly germline...
PURPOSE To estimate the risk of contralateral breast cancer (CBC) among women with germline pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2. METHODS The study population included 15,104 prospectively followed within CARRIERS treated ipsilateral surgery for invasive cancer. CBC was estimated PV carriers each gene compared without PVs a multivariate proportional hazard regression analysis accounting competing death adjusting patient tumor characteristics. primary analyses...
Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers1–5. However, variants of uncertain significance limit the utility test results. Thus, there is a need for functional characterization and classification all facilitate management individuals with these variants. Here we analysed possible single-nucleotide from exons 15 26 that encode DNA-binding domain hotspot pathogenic missense To enable this, used saturation...
Farnesoid X receptor (FXR) is a bile acid-activated transcription factor belonging to the nuclear superfamily. FXR highly expressed in liver and intestine crosstalk mediated by these two organs critical maintaining acid homeostasis. deficiency has been implicated many diseases. However, regulation of at genomic level not known. This study analyzed genome-wide binding mice treated with synthetic ligand (GW4064) chromatin immunoprecipitation coupled massively parallel sequencing (ChIP-seq)....
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...
Abstract Ovarian cancer is a clinically and molecularly heterogeneous disease. The driving forces behind this variability are unknown. Here, we report wide variation in the expression of DNA cytosine deaminase APOBEC3B, with elevated majority ovarian cell lines (three SDs above mean normal surface epithelial cells) high-grade primary cancers. APOBEC3B active nucleus several elicits biochemical preference for deamination cytosines 5′-TC dinucleotides. Importantly, examination whole-genome...
The prevalence of germline pathogenic mutations in a comprehensive panel cancer predisposition genes is not well-defined for patients with pancreatic ductal adenocarcinoma (PDAC). To estimate the frequency 22 genes, 96 unselected family history who were recruited to Mayo Clinic Pancreatic Cancer patient registry over 12-month period screened by next-generation sequencing. Fourteen 13 (13.5%) identified eight genes: four ATM, two BRCA2, CHEK2, and MSH6, one BARD1, BRCA1, FANCM, NBN. These...
Sequencing tests assaying panels of genes or whole exomes are widely available for cancer risk evaluation. However, methods classification variants resulting from this testing not well studied. We evaluated the ability a variant-classification methodology based on American College Medical Genetics and Genomics (ACMG) guidelines to define rate mutations uncertain significance (VUS) in 180 medically relevant genes, including all ACMG-designated reportable non-cancer-associated individuals who...
Understanding the gene-specific risks for development of breast cancer will lead to improved clinical care those carrying germline mutations in predisposition genes. We sought detail spectrum and refine risk estimates known proposed susceptibility Targeted massively-parallel sequencing was performed identify copy number variants 26 or genes 2134 BRCA1/2-negative women with familial (proband a family history ovarian cancer) from largely European-Caucasian multi-institutional cohort....
Abstract Common variants in 94 loci have been associated with breast cancer including 15 genome-wide significant associations ( P <5 × 10 −8 ) oestrogen receptor (ER)-negative and BRCA1 -associated risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 association studies (GWAS) consisting 4,939 cases 14,352 controls, combined 7,333 42,468 controls 15,252 mutation carriers genotyped on the iCOGS array. We four previously unidentified two...
<h3>Background</h3> BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family DNA repair proteins. Biallelic mutations in <i>BRIP1</i> are responsible for FANC J, and previous studies have also suggested that rare truncating variants associated with an increased risk breast cancer. These led to inclusion on targeted sequencing panels cancer prediction. <h3>Methods</h3> We evaluated a variant, p.Arg798Ter (rs137852986), 10...
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,...
To determine the sensitivity and specificity of genetic testing criteria for detection germline pathogenic variants in women with breast cancer.