Issues

To discover interactions between germline variants and somatic events in cancer, Carter and colleagues performed a genome-wide association study, evaluating genomic data from The Cancer Genome Atlas (TCGA) including more than 5,900 tumors and 22 cancer types. Association studies that compared tumor-specific SNPs identified loci that were significantly associated with specific tumor types, while association testing of SNPs in TCGA samples and the alteration status of 138 cancer driver genes identified 35 associations between 28 germline loci and 20 cancer driver genes. Analysis of mutational heterogeneity based on germline loci identified 20 candidate cancer driver genes, 15 of which had not previously been shown to be frequently mutated. In addition to providing a resource of germline–somatic interactions in cancer, these findings demonstrate that inherited risk variants can alter the somatic evolution of cancer. For details, please see the article by Carter and colleagues on page 410.