Computational approaches to identify functional genetic variants in cancer genomes

Abstract

The International Cancer Genome Consortium (ICGC) aims to catalog genomic abnormalities in tumors from 50 different cancer types. Genome sequencing reveals hundreds to thousands of somatic mutations in each tumor but only a minority of these drive tumor progression. We present the result of discussions within the ICGC on how to address the challenge of identifying mutations that contribute to oncogenesis, tumor maintenance or response to therapy, and recommend computational techniques to annotate somatic variants and predict their impact on cancer phenotype.

Figure 1

Scheme depicting the three main approaches routinely employed in the analysis of cancer somatic mutations, as reviewed in this perspective. Although there are important relationships of precedence between elements from different approaches, they do not necessarily correspond to sequential steps. Tools employed in each of the approaches are shown in the middle. Integrative pipelines refer to tools that facilitate the use of methods across all approaches (e.g., IntOGen-mutations pipeline).