3 years ago

Integrative clinical genomics of metastatic cancer

Integrative clinical genomics of metastatic cancer
Scott A. Tomlins, Erin Cobain, Marcin Cieślik, Moshe Talpaz, David C. Smith, Javed Siddiqui, Kenneth Offit, Rashmi Chugh, Xuhong Cao, Jessica Everett, Dan R. Robinson, Jeffrey Innis, Victoria Raymond, Robert J. Lonigro, Arul M. Chinnaiyan, Elena M. Stoffel, Chandan Kumar-Sinha, Pankaj Vats, Daniel F. Hayes, Laurence H. Baker, Erica Rabban, Lakshmi P. Kunju, Yi-Mi Wu, Rajen J. Mody, Ajjai Alva, David Lucas, Mark M. Zalupski, Ann F. Schott, Francis Worden, J. Scott Roberts, Joseph Vijai, Nithya Ramnath, Scott Schuetze
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.

Publisher URL: http://dx.doi.org/10.1038/nature23306

DOI: 10.1038/nature23306

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