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Nat Med. 2017 Jun;23(6):703-713. doi: 10.1038/nm.4333. Epub 2017 May 8.

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

Author information

1
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
2
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
3
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
4
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
5
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
6
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
7
Information Systems, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
8
Clinical Research Administration, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
9
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
10
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
11
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Abstract

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.

PMID:
28481359
PMCID:
PMC5461196
DOI:
10.1038/nm.4333
[Indexed for MEDLINE]
Free PMC Article

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