Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations across Pathways and Protein Complexes
Cancers exhibit extensive mutational heterogeneity and the resulting long tail phenomenon complicates the discovery of the genes and pathways that are significantly mutated in cancer. We perform a Pan-Cancer analysis of mutated networks in 3281 samples from 12 cancer types from The Cancer Genome Atl...
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| Language: | English |
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2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444046/ |
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pubmed-44440462015-08-01 Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations across Pathways and Protein Complexes Leiserson, Mark D.M. Vandin, Fabio Wu, Hsin-Ta Dobson, Jason R. Eldridge, Jonathan V. Thomas, Jacob L. Papoutsaki, Alexandra Kim, Younhun Niu, Beifang McLellan, Michael Lawrence, Michael S. Gonzalez-Perez, Abel Tamborero, David Cheng, Yuwei Ryslik, Gregory A. Lopez-Bigas, Nuria Getz, Gad Ding, Li Raphael, Benjamin J. Article Cancers exhibit extensive mutational heterogeneity and the resulting long tail phenomenon complicates the discovery of the genes and pathways that are significantly mutated in cancer. We perform a Pan-Cancer analysis of mutated networks in 3281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a novel algorithm to find mutated subnetworks that overcomes limitations of existing single gene and pathway/network approaches.. We identify 14 significantly mutated subnetworks that include 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. 2014-12-15 2015-02 /pmc/articles/PMC4444046/ /pubmed/25501392 http://dx.doi.org/10.1038/ng.3168 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Leiserson, Mark D.M. Vandin, Fabio Wu, Hsin-Ta Dobson, Jason R. Eldridge, Jonathan V. Thomas, Jacob L. Papoutsaki, Alexandra Kim, Younhun Niu, Beifang McLellan, Michael Lawrence, Michael S. Gonzalez-Perez, Abel Tamborero, David Cheng, Yuwei Ryslik, Gregory A. Lopez-Bigas, Nuria Getz, Gad Ding, Li Raphael, Benjamin J. |
| spellingShingle |
Leiserson, Mark D.M. Vandin, Fabio Wu, Hsin-Ta Dobson, Jason R. Eldridge, Jonathan V. Thomas, Jacob L. Papoutsaki, Alexandra Kim, Younhun Niu, Beifang McLellan, Michael Lawrence, Michael S. Gonzalez-Perez, Abel Tamborero, David Cheng, Yuwei Ryslik, Gregory A. Lopez-Bigas, Nuria Getz, Gad Ding, Li Raphael, Benjamin J. Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations across Pathways and Protein Complexes |
| author_facet |
Leiserson, Mark D.M. Vandin, Fabio Wu, Hsin-Ta Dobson, Jason R. Eldridge, Jonathan V. Thomas, Jacob L. Papoutsaki, Alexandra Kim, Younhun Niu, Beifang McLellan, Michael Lawrence, Michael S. Gonzalez-Perez, Abel Tamborero, David Cheng, Yuwei Ryslik, Gregory A. Lopez-Bigas, Nuria Getz, Gad Ding, Li Raphael, Benjamin J. |
| author_sort |
Leiserson, Mark D.M. |
| title |
Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations
across Pathways and Protein Complexes |
| title_short |
Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations
across Pathways and Protein Complexes |
| title_full |
Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations
across Pathways and Protein Complexes |
| title_fullStr |
Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations
across Pathways and Protein Complexes |
| title_full_unstemmed |
Pan-Cancer Network Analysis Identifies Combinations of Rare Somatic Mutations
across Pathways and Protein Complexes |
| title_sort |
pan-cancer network analysis identifies combinations of rare somatic mutations
across pathways and protein complexes |
| description |
Cancers exhibit extensive mutational heterogeneity and the resulting long tail
phenomenon complicates the discovery of the genes and pathways that are significantly
mutated in cancer. We perform a Pan-Cancer analysis of mutated networks in 3281 samples
from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a novel algorithm
to find mutated subnetworks that overcomes limitations of existing single gene and
pathway/network approaches.. We identify 14 significantly mutated subnetworks that include
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. |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444046/ |
| _version_ |
1613227669308047360 |