Kenneth Offit

SLC25A28 is a synthetic lethal vulnerability in nucleotide excision repair-deficient cancers

This study identifies SLC25A28 as a synthetic lethal target in NER-deficient cancers, showing its loss impairs cell viability and increases oxidative stress.

Cell-of-origin shapes tumor subtype in BRCA1-associated triple-negative breast cancer

This study identifies two cell-of-origin-driven subtypes of BRCA1-associated TNBC, showing that tumor subtype depends on the cell type initiating the cancer.

Integrated Clinicogenomic Risk Modeling for Metachronous Second Primary Cancers

The paper develops and validates a clinicogenomic risk model to predict second primary cancers in cancer survivors using genetic, clinical, and lifestyle factors.

The Impact of Breast Cancer Polygenic Risk Score Disclosure on Decisional Conflict Around Risk-Reducing Mastectomy in BRCA1/2 Carriers

This study examines if disclosing polygenic risk scores reduces decisional conflict in BRCA1/2 carriers considering risk-reducing mastectomy, finding decreased conflict and moderation by tolerance for ambiguity.

Exploring the genetic and epigenetic underpinnings of early-onset cancers: Variant prioritization for long read whole genome sequencing from family cancer pedigrees

This study uses long-read whole genome sequencing from family cancer pedigrees to prioritize genetic variants in early-onset cancers, identifying potential disease-causing mutations.

Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

This study examines differences in polygenic risk score distributions across European populations and shows how country-specific calibration can improve breast cancer risk prediction.

Novel ultra-rare exonic variants identified in a founder population implicate cadherins in schizophrenia

The paper identifies ultra-rare exonic variants in an Ashkenazi Jewish founder population, implicating cadherins in schizophrenia through recurrent mutations and altered purifying selection.

Genetic architectures of proximal and distal colorectal cancer are partly distinct

This study identifies 13 new genetic loci specific to proximal or distal colorectal cancer subtypes, revealing partly distinct genetic architectures for these tumor locations.

Inherited rare, deleterious variants in ATM increase lung adenocarcinoma risk

The paper identifies inherited rare, deleterious ATM variants as risk factors for lung adenocarcinoma, showing increased odds ratios in case-control studies and population cohorts.

Physical activity and risks of breast and colorectal cancer: A Mendelian randomization analysis

This study uses Mendelian randomization to show that higher physical activity levels are associated with lower risks of breast and colorectal cancer.

Oncologic Therapy Shapes the Fitness Landscape of ClonalHematopoiesis

The paper shows oncologic therapy increases clonal hematopoiesis with DDR mutations, which predicts risk of therapy-related myeloid neoplasms.

Towards automation of germline variant curation in clinical cancer genetics

PathoMAN automates germline variant curation using ACMG guidelines, achieving high concordance with expert curation and proposing refinements for better ClinVar reporting.

Case-control analysis identifies shared properties of rare germline variation in cancer predisposing genes

The paper analyzes rare germline variation in cancer predisposing genes across cancer patients and controls to identify shared mutation properties and candidate susceptibility genes.

High-depth whole genome sequencing of a large population-specific reference panel: Enhancing sensitivity, accuracy, and imputation

The paper sequenced a population-specific reference panel at high depth to improve imputation accuracy and variant filtering in the Ashkenazi Jewish population.

Novel pedigree analysis implicates DNA repair and chromatin remodeling in Multiple Myeloma risk

This paper introduces a new pedigree analysis method to identify risk variants for complex diseases, applying it to Multiple Myeloma and finding two genes associated with DNA repair and chromatin remodeling.

Tissue-specific Enrichment of Lymphoma Risk Loci in Regulatory Elements

The paper identifies lymphoma risk SNPs enriched in regulatory elements using a multiscale approach and develops an algorithm to analyze GWAS results.