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Nature. 2017 Aug 17;548(7667):297-303. doi: 10.1038/nature23306. Epub 2017 Aug 2.

Integrative clinical genomics of metastatic cancer.

Author information

1
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
2
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
3
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
4
Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.
5
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
6
Department of Health Behavior &Health Education, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
7
Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
8
Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA.
9
Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

Abstract

Metastasis is the primary cause of cancer-related deaths. Although The Cancer Genome Atlas has sequenced primary tumour types obtained from surgical resections, much less comprehensive molecular analysis is available from clinically acquired metastatic cancers. Here we perform whole-exome and -transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53, CDKN2A, PTEN, PIK3CA, and RB1. Putative pathogenic germline variants were present in 12.2% of cases of which 75% were related to defects in DNA repair. RNA sequencing complemented DNA sequencing to identify gene fusions, pathway activation, and immune profiling. Our results show that integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex molecular landscape and microenvironment of metastatic cancers.

PMID:
28783718
PMCID:
PMC5995337
DOI:
10.1038/nature23306
[Indexed for MEDLINE]
Free PMC Article

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