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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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
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.
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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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