Somatic Mutaome Profile in Human Cancer Tissues

Abstract

Somatic mutation is a major cause of cancer progression and varied responses of tumors against anticancer agents. Thus, wemust obtain and characterize genome-wide mutational profiles in individual cancer subtypes. The Cancer Genome Atlasdatabase includes large amounts of sequencing and omics data generated from diverse human cancer tissues. In the presentstudy, we integrated and analyzed the exome sequencing data from ∼3,000 tissue samples and summarized the majormutant genes in each of the diverse cancer subtypes and stages. Mutations were observed in most human genes (~23,000genes) with low frequency from an analysis of 11 major cancer subtypes. The majority of tissue samples harbored 20‒80different mutant genes, on average. Lung cancer samples showed a greater number of mutations in diverse genes than othercancer subtypes. Only a few genes were mutated with over 5% frequency in tissue samples. Interestingly, mutation frequencywas generally similar between non-metastatic and metastastic samples in most cancer subtypes. Among the 12 majormutations, the TP53, USH2A, TTN, and MUC16 genes were found to be frequent in most cancer types, while BRAF, FRG1B,PBRM1, and VHL showed lineage-specific mutation patterns. The present study provides a useful resource to understand thebroad spectrum of mutation frequencies in various cancer types.