1. Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes.
- Author
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Leiserson, Mark D M, Raphael, Benjamin J, Thomas, Jacob L, Vandin, Fabio, Ding, Li, Eldridge, Jonathan V, Kim, Younhun, McLellan, Michael, Gonzalez-Perez, Abel, Cheng, Yuwei, Dobson, Jason R, Niu, Beifang, Ryslik, Gregory A, Lopez-Bigas, Nuria, Wu, Hsin-Ta, Getz, Gad, Papoutsaki, Alexandra, Lawrence, Michael S, and Tamborero, David
- Subjects
CANCER ,DNA mutational analysis ,HETEROGENEITY ,SOMATIC hybrids ,PROTEINS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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