A5089800850- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Nutrition, Genetics, and Disease
- DNA Repair Mechanisms
- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Health Systems, Economic Evaluations, Quality of Life
- Statistical Methods in Clinical Trials
- PARP inhibition in cancer therapy
- Prostate Cancer Treatment and Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genetic Associations and Epidemiology
- Cancer-related Molecular Pathways
- Cardiac electrophysiology and arrhythmias
- Vehicle Dynamics and Control Systems
- Robotic Path Planning Algorithms
- Autonomous Vehicle Technology and Safety
- Gene expression and cancer classification
- Genomic variations and chromosomal abnormalities
- Genomics and Chromatin Dynamics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ovarian cancer diagnosis and treatment
University of Minnesota
2020-2023
Hormel (United States)
2020-2023
Mayo Clinic in Arizona
2019-2023
WinnMed
2018-2022
Mayo Clinic
2018-2022
Mayo Clinic in Florida
2018-2020
Ambry Genetics (United States)
2018
University of Glasgow
2015
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.
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....
To determine the sensitivity and specificity of genetic testing criteria for detection germline pathogenic variants in women with breast cancer.
Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in susceptibility genes and clinical relevance these are unclear. In this study, a prospective cohort mBC was used to determine mutation rates for (BC) predisposition genes, evaluate characteristics mutations, assess influence on patient outcome.
Abstract Background The risks of breast cancer in African American (AA) women associated with inherited mutations predisposition genes are not well defined. Thus, whether multigene germline hereditary testing panels applicable to this population is unknown. We assessed associations between panel-based and risk 5054 AA 4993 unaffected drawn from 10 epidemiologic studies. Methods Germline DNA samples were sequenced for 23 using a QIAseq multiplex amplicon panel. Prevalence odds ratios (ORs)...
Determination of the clinical relevance rare germline variants uncertain significance (VUSs) in BRCA2 cancer predisposition gene remains a challenge as result limited availability data for use classification models. However, laboratory-based functional derived from validated assays known sensitivity and specificity may influence interpretation VUSs. We evaluated 252 missense VUSs DNA-binding domain by using homology-directed DNA repair (HDR) assay identified 90 non-functional 162 functional....
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.
In studies of men European ancestry, rare pathogenic variants in DNA repair pathway genes have been shown to be associated with risk aggressive prostate cancer. The contribution coding variation cancer African ancestry has not established.
Inherited pathogenic variants in PALB2 are associated with increased risk of breast and pancreatic cancer. However, the functional clinical relevance many missense uncertain significance (VUS) identified through genetic testing is unclear. The ability patient-derived germline VUS to disrupt function was assessed identify potential relevance.The influence 84 on evaluated using a cellular homology directed DNA repair (HDR) assay impacting activity were further characterized secondary...
Abstract Purpose: To compare the clinical characteristics and overall survival (OS) of germline mutation carriers in homologous recombination repair (HRR) genes noncarriers with pancreatic ductal adenocarcinoma (PDAC). Experimental Design: Germline DNA from 3,078 patients PDAC enrolled a prospective registry at Mayo Clinic between 2000 2017 was analyzed for mutations 37 cancer predisposition genes. Characteristics OS eight (ATM, BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D) involved HRR...
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,...
To compare the prevalence of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC) and castrate-resistant (mCRPC) assess impact on progression to castration resistance overall survival.
Abstract Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk breast and ovarian cancer. A large number RAD51C missense uncertain significance (VUS) have been identified, but effects majority these on function cancer predisposition not established. Here, analysis 173 by a homology-directed repair (HDR) assay reconstituted RAD51C−/− cells identified 30 nonfunctional (deleterious) variants, including 18 hotspot within...
Loss-of-function variants in the BRCA1 and BRCA2 susceptibility genes predispose carriers to breast and/or ovarian cancer. The use of germline testing panels containing these has grown dramatically, but interpretation results been complicated by identification many sequence undefined cancer relevance, termed "Variants Uncertain Significance (VUS)." We have developed functional assays a statistical model called VarCall for classifying VUS. Here we describe multifactorial extension VarCall,...
Abstract The Wilms' tumor 1 (WT1) gene is well known as a chameleon gene. It plays role suppressor in but also acts an oncogene other cancers. Previously, our group reported that canonical AUG starting site for the WT1 protein (augWT1) suppressor, whereas CUG (cugWT1) functions oncogene. In this study, we report oncogenic of cugWT1 AOM/DSS-induced colon cancer mouse model and urethane-induced lung mice lacking cugWT1. Development chemically-induced tumors was significantly depressed...
<div>Abstract<p>Pathogenic protein-truncating variants of RAD51C, which plays an integral role in promoting DNA damage repair, increase the risk breast and ovarian cancer. A large number RAD51C missense uncertain significance (VUS) have been identified, but effects majority these on function cancer predisposition not established. Here, analysis 173 by a homology-directed repair (HDR) assay reconstituted RAD51C-/- cells identified 30 non-functional (deleterious) variants,...
<p>Supplementary Materials, References, Tables and Figures</p>
<p>Supplementary Materials, References, Tables and Figures</p>
Abstract Background: Pathogenic variants detected in multi-gene cancer predisposition panels are increasingly used to counsel women regarding their risk for breast cancer. However, the clinical implications of moderate penetrance genes (e.g. CHEK2, ATM) remain unclear. Breast MRI is indicated with a lifetime &gt;20%, and polygenic scores (PRS) based on common discovered recent genome-wide association studies (GWAS) may identify pathogenic CHEK2 ATM who above or below this level risk. PRS...
<div>Abstract<p>The <i>Wilms' tumor 1</i> (<i>WT1</i>) gene is well known as a chameleon gene. It plays role suppressor in Wilms' but also acts an oncogene other cancers. Previously, our group reported that canonical AUG starting site for the WT1 protein (augWT1) suppressor, whereas CUG (cugWT1) functions oncogene. In this study, we report oncogenic of cugWT1 AOM/DSS-induced colon cancer mouse model and urethane-induced lung mice lacking cugWT1....
<p>A, colon and lung cell lysates were subjected to Western blotting with antibodies detect phosphorylated WT1 (S64 or S68). B, immunofluorescence staining phosphorylation of human cancer tissue arrays, which included 9 cases normal tissue, 23 adjacent tissues. Results are shown as mean values {plus minus} S.D. (*p < 0.05, ** p 0.01 by one-way ANOVA Tukey's correction).</p>
<p>Supplementary materials and methods</p>
<div>Abstract<p>The <i>Wilms' tumor 1</i> (<i>WT1</i>) gene is well known as a chameleon gene. It plays role suppressor in Wilms' but also acts an oncogene other cancers. Previously, our group reported that canonical AUG starting site for the WT1 protein (augWT1) suppressor, whereas CUG (cugWT1) functions oncogene. In this study, we report oncogenic of cugWT1 AOM/DSS-induced colon cancer mouse model and urethane-induced lung mice lacking cugWT1....