Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas.

ABSTRACT: Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of recurrent somatic mutations to (1) predict somatic variants from tumor-only samples and (2) identify somatic-like germline variants for integrated analysis of tumor-normal DNA. Using data from 1769 patients from seven cancer types (bladder, glioblastoma, low-grade glioma, lung, melanoma, stomach, and pediatric glioma), we show that "somatic-like" germline variants are enriched for autosomal-dominant cancer-predisposition genes (p < 4.35 × 10^-15), including TP53. Our framework identifies germline and somatic nonsense

SUBMITTER: Madubata CJ 

PROVIDER: S-EPMC5677944 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature