Rohan Gnanaolivu
A5005519965- BRCA gene mutations in cancer
- Cancer Genomics and Diagnostics
- Nutrition, Genetics, and Disease
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- Pancreatic and Hepatic Oncology Research
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Health Systems, Economic Evaluations, Quality of Life
- Genetic Associations and Epidemiology
- PARP inhibition in cancer therapy
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Statistical Methods in Clinical Trials
- Prostate Cancer Treatment and Research
- Molecular Biology Techniques and Applications
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Viral Infections and Immunology Research
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- Metabolomics and Mass Spectrometry Studies
- Cardiac electrophysiology and arrhythmias
- Cancer-related gene regulation
Mayo Clinic in Florida
2017-2025
Mayo Clinic
2023-2024
WinnMed
2023-2024
Mayo Clinic in Arizona
2016-2023
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....
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...
To determine the sensitivity and specificity of genetic testing criteria for detection germline pathogenic variants in women with breast cancer.
This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC general population.
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....
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.
PURPOSE The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes women the general population over age 65 years is not well-defined. However, testing guidelines suggest that diagnosed with might have < 2.5% likelihood a PV high-penetrance gene. This study aimed to establish frequency PVs and remaining risks for each gene years. METHODS A total 26,707 from population-based studies (51.5% 48.5% unaffected) were tested Frequencies associations...
Diagnosing Mendelian and rare genetic conditions requires identifying phenotype-associated findings prioritizing likely disease-causing genes. This task is labor-intensive for molecular clinical geneticists, who must review extensive literature databases to link patient phenotypes with causal genotypes. The challenge further complicated by the large number of variants detected through next-generation sequencing, which impacts both diagnosis timelines care strategies. To address this, in...
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...
PURPOSE To determine the contribution of germline pathogenic variants (PVs) in hereditary cancer testing panel genes to invasive lobular carcinoma (ILC) breast. MATERIALS AND METHODS The study included 2,999 women with ILC from a population-based cohort and 3,796 undergoing clinical multigene (clinical cohort). Frequencies PVs breast predisposition ( ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, TP53) were compared between unaffected female controls infiltrating...
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...
Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) PC patients; however, the roles susceptibility gene mutations are unclear. We assessed for 15 cancers FDRs unselected probands.
Abstract Purpose To estimate the risk of contralateral breast cancer (CBC) among women in general population with germline pathogenic variants (PVs) ATM, BRCA1, BRCA2, CHEK2, and PALB2. Methods Among 15,104 prospectively followed within CARRIERS study treated ipsilateral surgery for invasive cancer, a subset 14,237 were identified from population-based studies. The CBC was estimated PV carriers each gene compared to without PVs multivariate proportional hazard regression analysis accounting...
Abstract Germline BRCA2 loss-of function (LOF) variants identified by clinical genetic testing predispose to breast, ovarian, prostate and pancreatic cancer. However, of uncertain significance (VUS) (n>4000) limit the use results. Thus, there is an urgent need for functional characterization classification all variants. Here we report on comprehensive saturation genome editing-based 97% possible single nucleotide (SNVs) in DNA Binding Domain hotspot pathogenic missense that encoded exons...
Human cancers present a significant public health challenge and require the discovery of novel drugs through translational research. Transcriptomics profiling data that describes molecular activities in tumors cancer cell lines are widely utilized for predicting anti-cancer drug responses. However, existing AI models face challenges due to noise transcriptomics lack biological interpretability. To overcome these limitations, we introduce VETE (Variational Explanatory Encoder), neural network...
Abstract Germline mutations in BRCA1 and BRCA2 (g BRCA1/2 ) are required for a PARP inhibitor therapy patients with HER2-negative (HER2−) advanced breast cancer (aBC). However, little is known about the prognostic impact of gBRCA1/2 aBC treated chemotherapy. This study aimed to investigate frequencies prognosis germline somatic HER2- receiving first chemotherapy setting. Patients their were retrospectively selected from prospective PRAEGNANT registry (NCT02338167). Genotyping 26...
Abstract The functional classification of a missense variant in cancer predisposition genes is often challenging due to how rare the observed population. When available, clinicians utilize combination family history, vitro assays and silico methods infer protein function. In methods, such as predictors (predict changes function) stability free energy) have been used help classify accordance with American College Medical Genetics Genomics (ACMG) guideline. To measure stability, many...