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A map of human cancer signaling

We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer-associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signaling regula...

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Autores principales: Cui, Qinghua, Ma, Yun, Jaramillo, Maria, Bari, Hamza, Awan, Arif, Yang, Song, Zhang, Simo, Liu, Lixue, Lu, Meng, O'Connor-McCourt, Maureen, Purisima, Enrico O, Wang, Edwin
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174632/
https://www.ncbi.nlm.nih.gov/pubmed/18091723
http://dx.doi.org/10.1038/msb4100200
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author Cui, Qinghua
Ma, Yun
Jaramillo, Maria
Bari, Hamza
Awan, Arif
Yang, Song
Zhang, Simo
Liu, Lixue
Lu, Meng
O'Connor-McCourt, Maureen
Purisima, Enrico O
Wang, Edwin
author_facet Cui, Qinghua
Ma, Yun
Jaramillo, Maria
Bari, Hamza
Awan, Arif
Yang, Song
Zhang, Simo
Liu, Lixue
Lu, Meng
O'Connor-McCourt, Maureen
Purisima, Enrico O
Wang, Edwin
author_sort Cui, Qinghua
collection PubMed
description We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer-associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signaling regulatory loops, whereas the cancer-associated methylated genes are enriched in negative signaling regulatory loops. We further characterized an overall picture of the cancer-signaling architectural and functional organization. From the network, we extracted an oncogene-signaling map, which contains 326 nodes, 892 links and the interconnections of mutated and methylated genes. The map can be decomposed into 12 topological regions or oncogene-signaling blocks, including a few ‘oncogene-signaling-dependent blocks' in which frequently used oncogene-signaling events are enriched. One such block, in which the genes are highly mutated and methylated, appears in most tumors and thus plays a central role in cancer signaling. Functional collaborations between two oncogene-signaling-dependent blocks occur in most tumors, although breast and lung tumors exhibit more complex collaborative patterns between multiple blocks than other cancer types. Benchmarking two data sets derived from systematic screening of mutations in tumors further reinforced our findings that, although the mutations are tremendously diverse and complex at the gene level, clear patterns of oncogene-signaling collaborations emerge recurrently at the network level. Finally, the mutated genes in the network could be used to discover novel cancer-associated genes and biomarkers.
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spelling pubmed-21746322008-01-04 A map of human cancer signaling Cui, Qinghua Ma, Yun Jaramillo, Maria Bari, Hamza Awan, Arif Yang, Song Zhang, Simo Liu, Lixue Lu, Meng O'Connor-McCourt, Maureen Purisima, Enrico O Wang, Edwin Mol Syst Biol Article We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer-associated genetically and epigenetically altered genes. We find that cancer mutated genes are enriched in positive signaling regulatory loops, whereas the cancer-associated methylated genes are enriched in negative signaling regulatory loops. We further characterized an overall picture of the cancer-signaling architectural and functional organization. From the network, we extracted an oncogene-signaling map, which contains 326 nodes, 892 links and the interconnections of mutated and methylated genes. The map can be decomposed into 12 topological regions or oncogene-signaling blocks, including a few ‘oncogene-signaling-dependent blocks' in which frequently used oncogene-signaling events are enriched. One such block, in which the genes are highly mutated and methylated, appears in most tumors and thus plays a central role in cancer signaling. Functional collaborations between two oncogene-signaling-dependent blocks occur in most tumors, although breast and lung tumors exhibit more complex collaborative patterns between multiple blocks than other cancer types. Benchmarking two data sets derived from systematic screening of mutations in tumors further reinforced our findings that, although the mutations are tremendously diverse and complex at the gene level, clear patterns of oncogene-signaling collaborations emerge recurrently at the network level. Finally, the mutated genes in the network could be used to discover novel cancer-associated genes and biomarkers. Nature Publishing Group 2007-12-18 /pmc/articles/PMC2174632/ /pubmed/18091723 http://dx.doi.org/10.1038/msb4100200 Text en Copyright © 2007, EMBO and Nature Publishing Group http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation or the creation of derivative works without specific permission.
spellingShingle Article
Cui, Qinghua
Ma, Yun
Jaramillo, Maria
Bari, Hamza
Awan, Arif
Yang, Song
Zhang, Simo
Liu, Lixue
Lu, Meng
O'Connor-McCourt, Maureen
Purisima, Enrico O
Wang, Edwin
A map of human cancer signaling
title A map of human cancer signaling
title_full A map of human cancer signaling
title_fullStr A map of human cancer signaling
title_full_unstemmed A map of human cancer signaling
title_short A map of human cancer signaling
title_sort map of human cancer signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174632/
https://www.ncbi.nlm.nih.gov/pubmed/18091723
http://dx.doi.org/10.1038/msb4100200
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