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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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Detalles Bibliográficos
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
Descripción
Sumario: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.