Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes

A partir de données issues du projet "The Cancer Genome Atlas" portant sur 3 281 échantillons tumoraux (12 types de cancer), cette étude identifie la présence fréquente de combinaisons de mutations somatiques rares relevant de voies de signalisation connues pour intervenir dans la cancérogenèse

Résumé en anglais

Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a new algorithm to find mutated subnetworks that overcomes the limitations of existing single-gene, pathway and network approaches. We identify 16 significantly mutated subnetworks that comprise well-known cancer signaling pathways as well as subnetworks with less characterized roles in cancer, including cohesin, condensin and others. Many of these subnetworks exhibit co-occurring mutations across samples. These subnetworks contain dozens of genes with rare somatic mutations across multiple cancers; many of these genes have additional evidence supporting a role in cancer. By illuminating these rare combinations of mutations, pan-cancer network analyses provide a roadmap to investigate new diagnostic and therapeutic opportunities across cancer types.