Emerging patterns of somatic mutations in cancer

Abstract

Recent advances in technological tools for massively parallel, high-throughput sequencing of DNA have enabled the comprehensive characterization of somatic mutations in a large number of tumour samples. In this Review, we describe recent cancer genomic studies that have assembled emerging views of the landscapes of somatic mutations through deep-sequencing analyses of the coding exomes and whole genomes in various cancer types. We discuss the comparative genomics of different cancers, including mutation rates and spectra, as well as the roles of environmental insults that influence these processes. We highlight the developing statistical approaches that are used to identify significantly mutated genes, and discuss the emerging biological and clinical insights from such analyses, as well as the future challenges of translating these genomic data into clinical impacts.

Figure 1. Frequent mutations of epigenetic regulators and pre-mRNA splicing machinery in cancers

Representative genes involved in (A) chromatin remodelling, histone and DNA methylation (Me), acetylation (Ac), and ubiquitination (Ub), and (B) pre-mRNA splicing that were identified to be recurrently mutated in various types of cancers by whole-exome and whole-genome sequencing are displayed. Predicted consequences of mutations, either gain of function (GOF) or loss of function (LOF), are also shown.