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Interpreting cancer genomes using systematic host perturbations by tumour virus proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations(1). Genome sequencing efforts...

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Autores principales: Rozenblatt-Rosen, Orit, Deo, Rahul C., Padi, Megha, Adelmant, Guillaume, Calderwood, Michael A., Rolland, Thomas, Grace, Miranda, Dricot, Amélie, Askenazi, Manor, Tavares, Maria, Pevzner, Sam, Abderazzaq, Fieda, Byrdsong, Danielle, Carvunis, Anne-Ruxandra, Chen, Alyce A., Cheng, Jingwei, Correll, Mick, Duarte, Melissa, Fan, Changyu, Feltkamp, Mariet C., Ficarro, Scott B., Franchi, Rachel, Garg, Brijesh K., Gulbahce, Natali, Hao, Tong, Holthaus, Amy M., James, Robert, Korkhin, Anna, Litovchick, Larisa, Mar, Jessica C., Pak, Theodore R., Rabello, Sabrina, Rubio, Renee, Shen, Yun, Singh, Saurav, Spangle, Jennifer M., Tasan, Murat, Wanamaker, Shelly, Webber, James T., Roecklein-Canfield, Jennifer, Johannsen, Eric, Barabási, Albert-László, Beroukhim, Rameen, Kieff, Elliott, Cusick, Michael E., Hill, David E., Münger, Karl, Marto, Jarrod A., Quackenbush, John, Roth, Frederick P., DeCaprio, James A., Vidal, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408847/
https://www.ncbi.nlm.nih.gov/pubmed/22810586
http://dx.doi.org/10.1038/nature11288
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author Rozenblatt-Rosen, Orit
Deo, Rahul C.
Padi, Megha
Adelmant, Guillaume
Calderwood, Michael A.
Rolland, Thomas
Grace, Miranda
Dricot, Amélie
Askenazi, Manor
Tavares, Maria
Pevzner, Sam
Abderazzaq, Fieda
Byrdsong, Danielle
Carvunis, Anne-Ruxandra
Chen, Alyce A.
Cheng, Jingwei
Correll, Mick
Duarte, Melissa
Fan, Changyu
Feltkamp, Mariet C.
Ficarro, Scott B.
Franchi, Rachel
Garg, Brijesh K.
Gulbahce, Natali
Hao, Tong
Holthaus, Amy M.
James, Robert
Korkhin, Anna
Litovchick, Larisa
Mar, Jessica C.
Pak, Theodore R.
Rabello, Sabrina
Rubio, Renee
Shen, Yun
Singh, Saurav
Spangle, Jennifer M.
Tasan, Murat
Wanamaker, Shelly
Webber, James T.
Roecklein-Canfield, Jennifer
Johannsen, Eric
Barabási, Albert-László
Beroukhim, Rameen
Kieff, Elliott
Cusick, Michael E.
Hill, David E.
Münger, Karl
Marto, Jarrod A.
Quackenbush, John
Roth, Frederick P.
DeCaprio, James A.
Vidal, Marc
author_facet Rozenblatt-Rosen, Orit
Deo, Rahul C.
Padi, Megha
Adelmant, Guillaume
Calderwood, Michael A.
Rolland, Thomas
Grace, Miranda
Dricot, Amélie
Askenazi, Manor
Tavares, Maria
Pevzner, Sam
Abderazzaq, Fieda
Byrdsong, Danielle
Carvunis, Anne-Ruxandra
Chen, Alyce A.
Cheng, Jingwei
Correll, Mick
Duarte, Melissa
Fan, Changyu
Feltkamp, Mariet C.
Ficarro, Scott B.
Franchi, Rachel
Garg, Brijesh K.
Gulbahce, Natali
Hao, Tong
Holthaus, Amy M.
James, Robert
Korkhin, Anna
Litovchick, Larisa
Mar, Jessica C.
Pak, Theodore R.
Rabello, Sabrina
Rubio, Renee
Shen, Yun
Singh, Saurav
Spangle, Jennifer M.
Tasan, Murat
Wanamaker, Shelly
Webber, James T.
Roecklein-Canfield, Jennifer
Johannsen, Eric
Barabási, Albert-László
Beroukhim, Rameen
Kieff, Elliott
Cusick, Michael E.
Hill, David E.
Münger, Karl
Marto, Jarrod A.
Quackenbush, John
Roth, Frederick P.
DeCaprio, James A.
Vidal, Marc
author_sort Rozenblatt-Rosen, Orit
collection PubMed
description Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations(1). Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations(2). However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations(3). To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer.
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spelling pubmed-34088472013-01-26 Interpreting cancer genomes using systematic host perturbations by tumour virus proteins Rozenblatt-Rosen, Orit Deo, Rahul C. Padi, Megha Adelmant, Guillaume Calderwood, Michael A. Rolland, Thomas Grace, Miranda Dricot, Amélie Askenazi, Manor Tavares, Maria Pevzner, Sam Abderazzaq, Fieda Byrdsong, Danielle Carvunis, Anne-Ruxandra Chen, Alyce A. Cheng, Jingwei Correll, Mick Duarte, Melissa Fan, Changyu Feltkamp, Mariet C. Ficarro, Scott B. Franchi, Rachel Garg, Brijesh K. Gulbahce, Natali Hao, Tong Holthaus, Amy M. James, Robert Korkhin, Anna Litovchick, Larisa Mar, Jessica C. Pak, Theodore R. Rabello, Sabrina Rubio, Renee Shen, Yun Singh, Saurav Spangle, Jennifer M. Tasan, Murat Wanamaker, Shelly Webber, James T. Roecklein-Canfield, Jennifer Johannsen, Eric Barabási, Albert-László Beroukhim, Rameen Kieff, Elliott Cusick, Michael E. Hill, David E. Münger, Karl Marto, Jarrod A. Quackenbush, John Roth, Frederick P. DeCaprio, James A. Vidal, Marc Nature Article Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations(1). Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations(2). However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations(3). To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer. 2012-07-26 /pmc/articles/PMC3408847/ /pubmed/22810586 http://dx.doi.org/10.1038/nature11288 Text en Users may view, print, copy, download and 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
spellingShingle Article
Rozenblatt-Rosen, Orit
Deo, Rahul C.
Padi, Megha
Adelmant, Guillaume
Calderwood, Michael A.
Rolland, Thomas
Grace, Miranda
Dricot, Amélie
Askenazi, Manor
Tavares, Maria
Pevzner, Sam
Abderazzaq, Fieda
Byrdsong, Danielle
Carvunis, Anne-Ruxandra
Chen, Alyce A.
Cheng, Jingwei
Correll, Mick
Duarte, Melissa
Fan, Changyu
Feltkamp, Mariet C.
Ficarro, Scott B.
Franchi, Rachel
Garg, Brijesh K.
Gulbahce, Natali
Hao, Tong
Holthaus, Amy M.
James, Robert
Korkhin, Anna
Litovchick, Larisa
Mar, Jessica C.
Pak, Theodore R.
Rabello, Sabrina
Rubio, Renee
Shen, Yun
Singh, Saurav
Spangle, Jennifer M.
Tasan, Murat
Wanamaker, Shelly
Webber, James T.
Roecklein-Canfield, Jennifer
Johannsen, Eric
Barabási, Albert-László
Beroukhim, Rameen
Kieff, Elliott
Cusick, Michael E.
Hill, David E.
Münger, Karl
Marto, Jarrod A.
Quackenbush, John
Roth, Frederick P.
DeCaprio, James A.
Vidal, Marc
Interpreting cancer genomes using systematic host perturbations by tumour virus proteins
title Interpreting cancer genomes using systematic host perturbations by tumour virus proteins
title_full Interpreting cancer genomes using systematic host perturbations by tumour virus proteins
title_fullStr Interpreting cancer genomes using systematic host perturbations by tumour virus proteins
title_full_unstemmed Interpreting cancer genomes using systematic host perturbations by tumour virus proteins
title_short Interpreting cancer genomes using systematic host perturbations by tumour virus proteins
title_sort interpreting cancer genomes using systematic host perturbations by tumour virus proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3408847/
https://www.ncbi.nlm.nih.gov/pubmed/22810586
http://dx.doi.org/10.1038/nature11288
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