Systematic discovery of germline cancer predisposition genes through the identification of somatic second hits
Submitted by susan on Wed, 2018-07-11 16:07
The genetic causes of cancer include both somatic mutations and inherited germline variants. Large-scale tumor sequencing has revolutionized the identification of somatic driver alterations but has had limited impact on the identification of cancer predisposition genes (CPGs). Here we present a statistical method, ALFRED, that tests Knudson’s two-hit hypothesis to systematically identify CPGs from cancer genome data. Applied to ~10,000 tumor exomes the approach identifies known and putative CPGs – including the chromatin modifier NSD1 – that contribute to cancer through a combination of rare germline variants and somatic loss-of-heterozygosity (LOH).
Main Topic:
Mark Content Private(Internal):
Email Alert:
1-13
2601
9
Publication Date:
04/07/2018