Somatic Mutation Rate as Determinant of Breast Cancer Penetrance in BRCA1/2 Familial Cases
Abstract
Analysis of how mutations accumulate in pretumor tissue, although widely presumed to occur, has been extremely difficult to study. This is principally because, with most such mutations being unique to individual cells within a tissue, their detection is technically challenging. In this study we propose to apply Single Cell Multiple Displacement Amplification (SCMDA) that we recently developed for high accuracy detection of a spectrum of mutations from single nucleotide substitutions to indels and aneuploidy in individual cells within pre-tumor tissues of women who inherited mutations in the BRCA1 or BRCA2 genes. We hypothesize that mutations from single nucleotide substitutions to indels, large genomic rearrangements, and aneuploidy accumulating as consequence of defects in homology dependent DNA repair in mammary epithelial cells are the underlying cause of increased cancer risk in these women. We further hypothesize that estrogen, which is known to generate metabolites that directly damage DNA, mechanistically acts as a modifier.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2021
- Accession Number
- AD1135348
Entities
People
- Jan Vijg
Organizations
- Albert Einstein College of Medicine