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Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically-defined tumor types, coupled wit...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461196/ https://www.ncbi.nlm.nih.gov/pubmed/28481359 http://dx.doi.org/10.1038/nm.4333 |
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author | Zehir, Ahmet Benayed, Ryma Shah, Ronak H. Syed, Aijazuddin Middha, Sumit Kim, Hyunjae R. Srinivasan, Preethi Gao, Jianjiong Chakravarty, Debyani Devlin, Sean M. Hellmann, Matthew D. Barron, David A. Schram, Alison M. Hameed, Meera Dogan, Snjezana Ross, Dara S. Hechtman, Jaclyn F. DeLair, Deborah F. Yao, JinJuan Mandelker, Diana L. Cheng, Donavan T. Chandramohan, Raghu Mohanty, Abhinita S. Ptashkin, Ryan N. Jayakumaran, Gowtham Prasad, Meera Syed, Mustafa H. Rema, Anoop Balakrishnan Liu, Zhen Y. Nafa, Khedoudja Borsu, Laetitia Sadowska, Justyna Casanova, Jacklyn Bacares, Ruben Kiecka, Iwona J. Razumova, Anna Son, Julie B. Stewart, Lisa Baldi, Tessara Mullaney, Kerry A. Al-Ahmadie, Hikmat Vakiani, Efsevia Abeshouse, Adam A. Penson, Alexander V. Jonsson, Philip Camacho, Niedzica Chang, Matthew T. Won, Helen H. Gross, Benjamin E. Kundra, Ritika Heins, Zachary J. Chen, Hsiao-Wei Phillips, Sarah Zhang, Hongxin Wang, Jiaojiao Ochoa, Angelica Wills, Jonathan Eubank, Michael Thomas, Stacy B. Gardos, Stuart M. Reales, Dalicia N. Galle, Jesse Durany, Robert Cambria, Roy Abida, Wassim Cercek, Andrea Feldman, Darren R. Gounder, Mrinal M. Hakimi, A. Ari Harding, James J. Iyer, Gopa Janjigian, Yelena Y. Jordan, Emmet J. Kelly, Ciara M. Lowery, Maeve A. Morris, Luc G.T. Omuro, Antonio M. Raj, Nitya Razavi, Pedram Shoushtari, Alexander N. Shukla, Neerav Soumerai, Tara E. Varghese, Anna M. Yaeger, Rona Coleman, Jonathan Bochner, Bernard Riely, Gregory J. Saltz, Leonard B. Scher, Howard I. Sabbatini, Paul J. Robson, Mark E. Klimstra, David S. Taylor, Barry S. Baselga, Jose Schultz, Nikolaus Hyman, David M. Arcila, Maria E. Solit, David B. Ladanyi, Marc Berger, Michael F. |
author_facet | Zehir, Ahmet Benayed, Ryma Shah, Ronak H. Syed, Aijazuddin Middha, Sumit Kim, Hyunjae R. Srinivasan, Preethi Gao, Jianjiong Chakravarty, Debyani Devlin, Sean M. Hellmann, Matthew D. Barron, David A. Schram, Alison M. Hameed, Meera Dogan, Snjezana Ross, Dara S. Hechtman, Jaclyn F. DeLair, Deborah F. Yao, JinJuan Mandelker, Diana L. Cheng, Donavan T. Chandramohan, Raghu Mohanty, Abhinita S. Ptashkin, Ryan N. Jayakumaran, Gowtham Prasad, Meera Syed, Mustafa H. Rema, Anoop Balakrishnan Liu, Zhen Y. Nafa, Khedoudja Borsu, Laetitia Sadowska, Justyna Casanova, Jacklyn Bacares, Ruben Kiecka, Iwona J. Razumova, Anna Son, Julie B. Stewart, Lisa Baldi, Tessara Mullaney, Kerry A. Al-Ahmadie, Hikmat Vakiani, Efsevia Abeshouse, Adam A. Penson, Alexander V. Jonsson, Philip Camacho, Niedzica Chang, Matthew T. Won, Helen H. Gross, Benjamin E. Kundra, Ritika Heins, Zachary J. Chen, Hsiao-Wei Phillips, Sarah Zhang, Hongxin Wang, Jiaojiao Ochoa, Angelica Wills, Jonathan Eubank, Michael Thomas, Stacy B. Gardos, Stuart M. Reales, Dalicia N. Galle, Jesse Durany, Robert Cambria, Roy Abida, Wassim Cercek, Andrea Feldman, Darren R. Gounder, Mrinal M. Hakimi, A. Ari Harding, James J. Iyer, Gopa Janjigian, Yelena Y. Jordan, Emmet J. Kelly, Ciara M. Lowery, Maeve A. Morris, Luc G.T. Omuro, Antonio M. Raj, Nitya Razavi, Pedram Shoushtari, Alexander N. Shukla, Neerav Soumerai, Tara E. Varghese, Anna M. Yaeger, Rona Coleman, Jonathan Bochner, Bernard Riely, Gregory J. Saltz, Leonard B. Scher, Howard I. Sabbatini, Paul J. Robson, Mark E. Klimstra, David S. Taylor, Barry S. Baselga, Jose Schultz, Nikolaus Hyman, David M. Arcila, Maria E. Solit, David B. Ladanyi, Marc Berger, Michael F. |
author_sort | Zehir, Ahmet |
collection | PubMed |
description | Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically-defined tumor types, coupled with an expanding portfolio of molecularly-targeted therapies, demands flexible and comprehensive approaches to profile clinically significant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative utilizing a comprehensive assay, MSK-IMPACT, through which we have compiled matched tumor and normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel non-coding alterations, and mutational signatures that were shared among common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible. |
format | Online Article Text |
id | pubmed-5461196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
spelling | pubmed-54611962017-11-08 Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients Zehir, Ahmet Benayed, Ryma Shah, Ronak H. Syed, Aijazuddin Middha, Sumit Kim, Hyunjae R. Srinivasan, Preethi Gao, Jianjiong Chakravarty, Debyani Devlin, Sean M. Hellmann, Matthew D. Barron, David A. Schram, Alison M. Hameed, Meera Dogan, Snjezana Ross, Dara S. Hechtman, Jaclyn F. DeLair, Deborah F. Yao, JinJuan Mandelker, Diana L. Cheng, Donavan T. Chandramohan, Raghu Mohanty, Abhinita S. Ptashkin, Ryan N. Jayakumaran, Gowtham Prasad, Meera Syed, Mustafa H. Rema, Anoop Balakrishnan Liu, Zhen Y. Nafa, Khedoudja Borsu, Laetitia Sadowska, Justyna Casanova, Jacklyn Bacares, Ruben Kiecka, Iwona J. Razumova, Anna Son, Julie B. Stewart, Lisa Baldi, Tessara Mullaney, Kerry A. Al-Ahmadie, Hikmat Vakiani, Efsevia Abeshouse, Adam A. Penson, Alexander V. Jonsson, Philip Camacho, Niedzica Chang, Matthew T. Won, Helen H. Gross, Benjamin E. Kundra, Ritika Heins, Zachary J. Chen, Hsiao-Wei Phillips, Sarah Zhang, Hongxin Wang, Jiaojiao Ochoa, Angelica Wills, Jonathan Eubank, Michael Thomas, Stacy B. Gardos, Stuart M. Reales, Dalicia N. Galle, Jesse Durany, Robert Cambria, Roy Abida, Wassim Cercek, Andrea Feldman, Darren R. Gounder, Mrinal M. Hakimi, A. Ari Harding, James J. Iyer, Gopa Janjigian, Yelena Y. Jordan, Emmet J. Kelly, Ciara M. Lowery, Maeve A. Morris, Luc G.T. Omuro, Antonio M. Raj, Nitya Razavi, Pedram Shoushtari, Alexander N. Shukla, Neerav Soumerai, Tara E. Varghese, Anna M. Yaeger, Rona Coleman, Jonathan Bochner, Bernard Riely, Gregory J. Saltz, Leonard B. Scher, Howard I. Sabbatini, Paul J. Robson, Mark E. Klimstra, David S. Taylor, Barry S. Baselga, Jose Schultz, Nikolaus Hyman, David M. Arcila, Maria E. Solit, David B. Ladanyi, Marc Berger, Michael F. Nat Med Article Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically-defined tumor types, coupled with an expanding portfolio of molecularly-targeted therapies, demands flexible and comprehensive approaches to profile clinically significant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative utilizing a comprehensive assay, MSK-IMPACT, through which we have compiled matched tumor and normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel non-coding alterations, and mutational signatures that were shared among common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible. 2017-05-08 2017-06 /pmc/articles/PMC5461196/ /pubmed/28481359 http://dx.doi.org/10.1038/nm.4333 Text en 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 |
spellingShingle | Article Zehir, Ahmet Benayed, Ryma Shah, Ronak H. Syed, Aijazuddin Middha, Sumit Kim, Hyunjae R. Srinivasan, Preethi Gao, Jianjiong Chakravarty, Debyani Devlin, Sean M. Hellmann, Matthew D. Barron, David A. Schram, Alison M. Hameed, Meera Dogan, Snjezana Ross, Dara S. Hechtman, Jaclyn F. DeLair, Deborah F. Yao, JinJuan Mandelker, Diana L. Cheng, Donavan T. Chandramohan, Raghu Mohanty, Abhinita S. Ptashkin, Ryan N. Jayakumaran, Gowtham Prasad, Meera Syed, Mustafa H. Rema, Anoop Balakrishnan Liu, Zhen Y. Nafa, Khedoudja Borsu, Laetitia Sadowska, Justyna Casanova, Jacklyn Bacares, Ruben Kiecka, Iwona J. Razumova, Anna Son, Julie B. Stewart, Lisa Baldi, Tessara Mullaney, Kerry A. Al-Ahmadie, Hikmat Vakiani, Efsevia Abeshouse, Adam A. Penson, Alexander V. Jonsson, Philip Camacho, Niedzica Chang, Matthew T. Won, Helen H. Gross, Benjamin E. Kundra, Ritika Heins, Zachary J. Chen, Hsiao-Wei Phillips, Sarah Zhang, Hongxin Wang, Jiaojiao Ochoa, Angelica Wills, Jonathan Eubank, Michael Thomas, Stacy B. Gardos, Stuart M. Reales, Dalicia N. Galle, Jesse Durany, Robert Cambria, Roy Abida, Wassim Cercek, Andrea Feldman, Darren R. Gounder, Mrinal M. Hakimi, A. Ari Harding, James J. Iyer, Gopa Janjigian, Yelena Y. Jordan, Emmet J. Kelly, Ciara M. Lowery, Maeve A. Morris, Luc G.T. Omuro, Antonio M. Raj, Nitya Razavi, Pedram Shoushtari, Alexander N. Shukla, Neerav Soumerai, Tara E. Varghese, Anna M. Yaeger, Rona Coleman, Jonathan Bochner, Bernard Riely, Gregory J. Saltz, Leonard B. Scher, Howard I. Sabbatini, Paul J. Robson, Mark E. Klimstra, David S. Taylor, Barry S. Baselga, Jose Schultz, Nikolaus Hyman, David M. Arcila, Maria E. Solit, David B. Ladanyi, Marc Berger, Michael F. Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients |
title | Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients |
title_full | Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients |
title_fullStr | Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients |
title_full_unstemmed | Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients |
title_short | Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients |
title_sort | mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461196/ https://www.ncbi.nlm.nih.gov/pubmed/28481359 http://dx.doi.org/10.1038/nm.4333 |
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