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Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients

2017; Nature Portfolio; Volume: 23; Issue: 6 Linguagem: Inglês

10.1038/nm.4333

1546-170X

Ahmet Zehir, Ryma Benayed, Ronak Shah, Aijazuddin Syed, Sumit Middha, Hyunjae R. Kim, Preethi Srinivasan, Jianjiong Gao, Debyani Chakravarty, Sean M. Devlin, Matthew D. Hellmann, David Barron, Alison M. Schram, Meera Hameed, Snjezana Doğan, Dara S. Ross, Jaclyn F. Hechtman, Deborah F. DeLair, JinJuan Yao, Diana Mandelker, Donavan T. Cheng, Raghu Chandramohan, Abhinita Mohanty, Ryan Ptashkin, Gowtham Jayakumaran, Meera Prasad, Mustafa Syed, Anoop Balakrishnan Rema, Zhen Y. Liu, Khédoudja Nafa, Laetitia Borsu, Justyna Sadowska, Jacklyn Casanova, Ruben Bacares, Iwona Kiecka, Anna Razumova, Julie B Son, Lisa Stewart, Tessara Baldi, Kerry Mullaney, Hikmat Al‐Ahmadie, Efsevia Vakiani, Adam Abeshouse, Alexander Penson, Philip Jonsson, Niedzica Camacho, Matthew T. Chang, Helen Won, Benjamin Groß, Ritika Kundra, Zachary Heins, Hsiao‐Wei Chen, Sarah Phillips, Hongxin Zhang, Jiaojiao Wang, Angelica Ochoa, Jonathan Wills, Michael Eubank, Stacy B. Thomas, Stuart M. Gardos, Dalicia N. Reales, Jesse Galle, Robert Durany, Roy Cambria, Wassim Abida, Andrea Cercek, Darren R. Feldman, Mrinal M. Gounder, A. Ari Hakimi, James J. Harding, Gopa Iyer, Yelena Y. Janjigian, Emmet Jordan, Ciara M. Kelly, Maeve A. Lowery, Luc G.T. Morris, Antonio Omuro, Nitya Raj, Pedram Razavi, Alexander N. Shoushtari, Neerav Shukla, Tara E. Soumerai, Anna M. Varghese, Rona Yaeger, Jonathan Coleman, Bernard H. Bochner, Gregory J. Riely, Leonard B. Saltz, Howard I. Scher, Paul Sabbatini, Mark E. Robson, David S. Klimstra, Barry S. Taylor, José Baselga, Nikolaus Schultz, David M. Hyman, Maria E. Arcila, David B. Solit, Marc Ladanyi, Michael F. Berger,

Epigenetics and DNA Methylation

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 relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched 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 noncoding alterations, and mutational signatures that were shared by 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.