Global Characterization of Protein Altering Mutations in Prostate Cancer
Abstract
The research supported by this award aims to use a new generation of technologies for DNA sequencing to comprehensively scan the genomes of a series of prostate cancers for small mutations that disrupt protein-coding sequences. Our specific aims are as follows: (1) To carry out the genome-wide identification of nonsynonymous mutations in a limited number of prostate metastases using second generation technologies for targeted capture and sequencing; (2) To evaluate the mutational histories of individual mutations within the progression of the cancer in which it was observed, and to assess the prevalence of candidate cancer genes observed here in prostate cancer. (3) To perform integrative analyses of somatic mutation with gene expression and copy number change data collected on the same samples. To date, we have performed high-quality whole exome sequencing of 23 prostate cancers derived from 16 different lethal metastatic tumors and 3 high grade primary carcinomas. We have found that a subset of prostate cancers that exhibit a clear hypermutator phenotype with respect to point mutations, with potential implications for resistance to cancer therapeutics. We have also identified a subset of genes that appear to be recurrently mutated in our discovery set, and are therefore strong candidates for additional investigation for potential relevance to prostate cancer initiation or progression to metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2011
- Accession Number
- ADA549529
Entities
People
- Jay Shendure
Organizations
- University of Washington