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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We gratefully acknowledge C. England, J. Somar, T. Malbari, P. Salazar, S. Islam, E. Gallagher, I. Rijo, N. Mensah, G. Lukose, T. Mitchell, A. Yannes, Y. Chekaluk, G. Jour, N. Sadri, K. Tian, C. Pagan, J.K. Killian, D. Alex, J. Gomez-Gelvez, C. Ho, S. Naupari, J. Arlequin, C. Carvajal, L. Tovar Ramirez, J. Bakas, P. Sukhadia, E. Paraiso and J. Rudolph for their important contributions. This study was supported by the MSK Cancer Center Support Grant (P30 CA008748), Cycle for Survival, the Farmer Family Foundation, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology.
The authors declare no competing financial interests.
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Zehir, A., Benayed, R., Shah, R. et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 23, 703–713 (2017). https://doi.org/10.1038/nm.4333
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