ID

45655

Descrizione

Principal Investigator: San Ming Wang, MD, University of Nebraska Medical Center, NE, USA MeSH: Breast Neoplasms,Genes, BRCA1,Germ-Line Mutation https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001243 Our study addressed a specific question in NCI RFA-CA-12-022: "What underlying causal events - e.g., genetic, epigenetic, biologic, behavioral, or environmental - allow certain individuals to survive beyond the expected limits of otherwise highly lethal cancers?". A germline mutation in BRCA1 (BRCA1+) is the most penetrant genetic predisposition for breast cancer. Nevertheless, a portion of BRCA1+ carriers does not develop breast cancer in their lifetime, suggesting that the genetic predisposition can be antagonized by resistant factors. BRCA1+ was inherited from an ancestor of the carrier family thousand years ago. We hypothesize that evolution could select certain genetic components to suppress oncogenesis caused by the predisposition. We compared germline variants in all genes in 27 pairs of breast cancer-unaffected and -affected BRCA1+ carriers, each pair inherited the same BRCA1+. We identified 12 deleterious variants enriched in breast cancer-unaffected carriers, all are common variants. A variant rs3735400 is located in ANLN, a cytokinesis-essential gene. Overexpression of variant-containing ANLN and suppressed expression of endogenous ANLN decrease ANLN nuclear localization and delay cell growth. Our findings suggest that common variants can be selected to resist oncogenesis imposed by BRCA1+.

collegamento

dbGaP study = phs001243

Keywords

versioni (1)

1. 21/03/23 21/03/23 - Simon Heim

Titolare del copyright

San Ming Wang, MD, University of Nebraska Medical Center, NE, USA

Caricato su

21 marzo 2023

DOI

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