Integrative clinical genomics of metastatic cancer

Dan R. Robinson, Yi-Mi Wu, Robert J. Lonigro, Pankaj Vats, Erin Cobain, Jessica Everett, Xuhong Cao, Erica Rabban, Chandan Kumar-Sinha, Victoria Raymond, Scott Schuetze, Ajjai Alva, Javed Siddiqui, Rashmi Chugh, Francis Worden, Mark M. Zalupski, Jeffrey Innis, Rajen J. Mody, Scott A. Tomlins, David Lucas, Laurence H. Baker, Nithya Ramnath, Ann F. Schott, Daniel F. Hayes, Joseph Vijai, Kenneth Offit, Elena M. Stoffel, J. Scott Roberts, David C. Smith, Lakshmi P. Kunju, Moshe Talpaz, Marcin Cieślik and Arul M. Chinnaiyan ()
Additional contact information
Dan R. Robinson: Michigan Center for Translational Pathology, University of Michigan
Yi-Mi Wu: Michigan Center for Translational Pathology, University of Michigan
Robert J. Lonigro: Michigan Center for Translational Pathology, University of Michigan
Pankaj Vats: Michigan Center for Translational Pathology, University of Michigan
Erin Cobain: University of Michigan
Jessica Everett: University of Michigan
Xuhong Cao: Michigan Center for Translational Pathology, University of Michigan
Erica Rabban: Michigan Center for Translational Pathology, University of Michigan
Chandan Kumar-Sinha: Michigan Center for Translational Pathology, University of Michigan
Victoria Raymond: University of Michigan
Scott Schuetze: University of Michigan
Ajjai Alva: University of Michigan
Javed Siddiqui: Michigan Center for Translational Pathology, University of Michigan
Rashmi Chugh: University of Michigan
Francis Worden: University of Michigan
Mark M. Zalupski: University of Michigan
Jeffrey Innis: University of Michigan
Rajen J. Mody: University of Michigan
Scott A. Tomlins: Michigan Center for Translational Pathology, University of Michigan
David Lucas: University of Michigan
Laurence H. Baker: University of Michigan
Nithya Ramnath: University of Michigan
Ann F. Schott: University of Michigan
Daniel F. Hayes: University of Michigan
Joseph Vijai: Memorial Sloan Kettering Cancer Center
Kenneth Offit: Memorial Sloan Kettering Cancer Center
Elena M. Stoffel: University of Michigan
J. Scott Roberts: School of Public Health, University of Michigan
David C. Smith: University of Michigan
Lakshmi P. Kunju: Michigan Center for Translational Pathology, University of Michigan
Moshe Talpaz: Comprehensive Cancer Center, University of Michigan
Marcin Cieślik: Michigan Center for Translational Pathology, University of Michigan
Arul M. Chinnaiyan: Michigan Center for Translational Pathology, University of Michigan

Nature, 2017, vol. 548, issue 7667, 297-303

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature23306

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