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Interpreting pathways to discover cancer driver genes with Moonlight

Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. W...

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Autores principales: Colaprico, Antonio, Olsen, Catharina, Bailey, Matthew H., Odom, Gabriel J., Terkelsen, Thilde, Silva, Tiago C., Olsen, André V., Cantini, Laura, Zinovyev, Andrei, Barillot, Emmanuel, Noushmehr, Houtan, Bertoli, Gloria, Castiglioni, Isabella, Cava, Claudia, Bontempi, Gianluca, Chen, Xi Steven, Papaleo, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941958/
https://www.ncbi.nlm.nih.gov/pubmed/31900418
http://dx.doi.org/10.1038/s41467-019-13803-0
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author Colaprico, Antonio
Olsen, Catharina
Bailey, Matthew H.
Odom, Gabriel J.
Terkelsen, Thilde
Silva, Tiago C.
Olsen, André V.
Cantini, Laura
Zinovyev, Andrei
Barillot, Emmanuel
Noushmehr, Houtan
Bertoli, Gloria
Castiglioni, Isabella
Cava, Claudia
Bontempi, Gianluca
Chen, Xi Steven
Papaleo, Elena
author_facet Colaprico, Antonio
Olsen, Catharina
Bailey, Matthew H.
Odom, Gabriel J.
Terkelsen, Thilde
Silva, Tiago C.
Olsen, André V.
Cantini, Laura
Zinovyev, Andrei
Barillot, Emmanuel
Noushmehr, Houtan
Bertoli, Gloria
Castiglioni, Isabella
Cava, Claudia
Bontempi, Gianluca
Chen, Xi Steven
Papaleo, Elena
author_sort Colaprico, Antonio
collection PubMed
description Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.
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spelling pubmed-69419582020-01-06 Interpreting pathways to discover cancer driver genes with Moonlight Colaprico, Antonio Olsen, Catharina Bailey, Matthew H. Odom, Gabriel J. Terkelsen, Thilde Silva, Tiago C. Olsen, André V. Cantini, Laura Zinovyev, Andrei Barillot, Emmanuel Noushmehr, Houtan Bertoli, Gloria Castiglioni, Isabella Cava, Claudia Bontempi, Gianluca Chen, Xi Steven Papaleo, Elena Nat Commun Article Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions. Nature Publishing Group UK 2020-01-03 /pmc/articles/PMC6941958/ /pubmed/31900418 http://dx.doi.org/10.1038/s41467-019-13803-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Colaprico, Antonio
Olsen, Catharina
Bailey, Matthew H.
Odom, Gabriel J.
Terkelsen, Thilde
Silva, Tiago C.
Olsen, André V.
Cantini, Laura
Zinovyev, Andrei
Barillot, Emmanuel
Noushmehr, Houtan
Bertoli, Gloria
Castiglioni, Isabella
Cava, Claudia
Bontempi, Gianluca
Chen, Xi Steven
Papaleo, Elena
Interpreting pathways to discover cancer driver genes with Moonlight
title Interpreting pathways to discover cancer driver genes with Moonlight
title_full Interpreting pathways to discover cancer driver genes with Moonlight
title_fullStr Interpreting pathways to discover cancer driver genes with Moonlight
title_full_unstemmed Interpreting pathways to discover cancer driver genes with Moonlight
title_short Interpreting pathways to discover cancer driver genes with Moonlight
title_sort interpreting pathways to discover cancer driver genes with moonlight
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941958/
https://www.ncbi.nlm.nih.gov/pubmed/31900418
http://dx.doi.org/10.1038/s41467-019-13803-0
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