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Integrative clinical genomics of metastatic cancer.
Robinson, Dan R; Wu, Yi-Mi; Lonigro, Robert J; Vats, Pankaj; Cobain, Erin; Everett, Jessica; Cao, Xuhong; Rabban, Erica; Kumar-Sinha, Chandan; Raymond, Victoria; Schuetze, Scott; Alva, Ajjai; Siddiqui, Javed; Chugh, Rashmi; Worden, Francis; Zalupski, Mark M; Innis, Jeffrey; Mody, Rajen J; Tomlins, Scott A; Lucas, David; Baker, Laurence H; Ramnath, Nithya; Schott, Ann F; Hayes, Daniel F; Vijai, Joseph; Offit, Kenneth; Stoffel, Elena M; Roberts, J Scott; Smith, David C; Kunju, Lakshmi P; Talpaz, Moshe; Cieslik, Marcin; Chinnaiyan, Arul M.
Affiliation
  • Robinson DR; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Wu YM; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Lonigro RJ; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Vats P; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Cobain E; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Everett J; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Cao X; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Rabban E; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Kumar-Sinha C; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Raymond V; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Schuetze S; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Alva A; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Siddiqui J; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Chugh R; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Worden F; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Zalupski MM; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Innis J; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Mody RJ; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Tomlins SA; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Lucas D; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Baker LH; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Ramnath N; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Schott AF; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Hayes DF; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Vijai J; Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Offit K; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Stoffel EM; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Roberts JS; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Smith DC; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Kunju LP; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • Talpaz M; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • Cieslik M; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Chinnaiyan AM; Department of Health Behavior &Health Education, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nature ; 548(7667): 297-303, 2017 08 17.
Article in En | MEDLINE | ID: mdl-28783718
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genomics / Genetics, Medical / Neoplasm Metastasis Limits: Adult / Female / Humans / Male Language: En Journal: Nature Year: 2017 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genomics / Genetics, Medical / Neoplasm Metastasis Limits: Adult / Female / Humans / Male Language: En Journal: Nature Year: 2017 Document type: Article Affiliation country: United States