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Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes
Oleh:
Leiserson, Mark D M
;
Vandin, Fabio
;
Hsin-Ta, Wu
;
Dobson, Jason R
;
Eldridge, Jonathan V
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Nature Genetics vol. 47 no. 02 (Feb. 2015)
,
page 106–114.
Ketersediaan
Perpustakaan FK
Nomor Panggil:
N12.K
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
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.
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