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

Authors:
James J Harding, MD
James J Harding, MD
Memorial Sloan Kettering Cancer Center
Assistant Attending
Medical Oncology
United States
Ahmet Zehir Ryma Benayed Ronak H Shah Aijazuddin Syed Sumit Middha Hyunjae R Kim Preethi Srinivasan Jianjiong Gao Debyani Chakravarty Sean M Devlin Matthew D Hellmann David A Barron Alison M Schram Meera Hameed Snjezana Dogan Dara S Ross Jaclyn F Hechtman Deborah F DeLair JinJuan Yao Diana L Mandelker Donavan T Cheng Raghu Chandramohan Abhinita S Mohanty Ryan N Ptashkin Gowtham Jayakumaran Meera Prasad Mustafa H Syed Anoop Balakrishnan Rema Zhen Y Liu Khedoudja Nafa Laetitia Borsu Justyna Sadowska Jacklyn Casanova Ruben Bacares Iwona J Kiecka Anna Razumova Julie B Son Lisa Stewart Tessara Baldi Kerry A Mullaney Hikmat Al-Ahmadie Efsevia Vakiani Adam A Abeshouse Alexander V Penson Philip Jonsson Niedzica Camacho Matthew T Chang Helen H Won Benjamin E Gross Ritika Kundra Zachary J 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 Gopa Iyer Yelena Y Janjigian Emmet J Jordan Ciara M Kelly Maeve A Lowery Luc G T Morris Antonio M Omuro Nitya Raj Pedram Razavi Alexander N Shoushtari Neerav Shukla Tara E Soumerai Anna M Varghese Rona Yaeger Jonathan Coleman Bernard Bochner Gregory J Riely Leonard B Saltz Howard I Scher Paul J Sabbatini Mark E Robson David S Klimstra Barry S Taylor Jose Baselga Nikolaus Schultz David M Hyman Maria E Arcila David B Solit Marc Ladanyi Michael F Berger

Nat Med 2017 Jun 8;23(6):703-713. Epub 2017 May 8.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

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.

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http://www.nature.com/doifinder/10.1038/nm.4333
Publisher Site
http://dx.doi.org/10.1038/nm.4333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5461196PMC
June 2017
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