Somatic Mosaicism for Cancer Predisposition Genes and Pancreatic Cancer
Abstract
Somatic mosaicism refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a postzygotic mutation. Unlike inherited mutations in which the variant allele is present in all cells in the body, somatic mosaic mutations may affect only a subset of cells and may not be passed on to their progeny. Somatic mosaicism is a clinically relevant phenomenon for a variety of human diseases, including rare and common cancers. However, the extent to which somatic mosaicism for PDA cancer predisposition genes accounts for PDA incidence is unknown. In this proposal we propose two specific aims to address this topic. First, we will determine the extent to which driver genes are somatically mutated in multiple matched normal tissues previously collected from >100 clinically annotated PDA patients who underwent rapid autopsy. Second, we will determine the extent to which somatic mosaicism for driver gene mutations are associated with pancreatic carcinogenesis. Towards these goals we have extracted genomic DNA of 772 normal tissues from103 individuals, the majority of which died of pancreatic cancer or had a strong family history of cancer. Thus far all tissues from 21 of these patients have undergone targeted sequencing using a 468 gene panel and are currently undergoing bioinformatics analysis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2017
- Accession Number
- AD1050382
Entities
People
- Christine A Iacobuzio-Donahue
Organizations
- Sloan-Kettering Institute