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Cited by 863Cancer Genomics and DiagnosticsGenomics and Rare DiseasesBRCA gene mutations in cancer

Integrative clinical genomics of metastatic cancer

Open access
Robinson, Dan R., Wu, Yi-Mi, Lonigro, Robert J., Vats, Pankaj, Cobain, Erin, Everett, Jessica, Cao, Xuhong, Rabban, Erica +25 more·2017·Nature
DOI 10.1038/nature23306PMC PMC5995337
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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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  • These two mutually exclusive states likely account for the reversibility in chromosome missegregation rates seen in primary tumors and metastases.

    “These two mutually exclusive states, which were recently observed in a pan-cancer genomic analysis of metastatic tumors41, likely account for the reversibility in chromosome missegregation rates seen in primary tumors and metastases”

    From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [41]

  • CIN drives the subset of human metastases characterized by EMT and inflammation.

    “It also leads us to suggest that CIN drives the subset of human metastases characterized by EMT and inflammation41.”

    From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [41]

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Sorted by citations

Authors
Robinson, D. R., Wu, Y.-M., Lonigro, R. J., Vats, P., Cobain, E., Everett, J., Cao, X., Rabban, E., Kumar-Sinha, C., Raymond, V., Schuetze, S., Alva, A., Siddiqui, J., Chugh, R., Worden, F., Zalupski, M. M., Innis, J., Mody, R. J., Tomlins, S. A., Lucas, D., Baker, L. H., Ramnath, N., Schott, A. F., Hayes, D. F., Vijai, J., Offit, K., Stoffel, E. M., Roberts, J. S., Smith, D. C., Kunju, L. P., Talpaz, M., Cieślik, M., & Chinnaiyan, A. M.
Affiliations
  • University of Michigan (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Chinnaiyan, Arul M.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-08
Volume
548
Issue
7667
Pages
297-303
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature23306
PMC
PMC5995337
OpenAlex
W2741363425
Cited by
863
References
7
Citations by year
2026: 37 · 2025: 64 · 2024: 89 · 2023: 120 · 2022: 109 · 2021: 123 · 2020: 105 · 2019: 108 · 2018: 89 · 2017: 17 · 2014: 1
FWCI
29.40
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute for Health and Care Research
  • National Institutes of Health
  • National Human Genome Research Institute (UM1HG006508)
  • National Cancer Institute (U01CA214170, P30CA046592, P50CA186786)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Keywords
metastatic cancer, solid tumors, somatic mutations, TP53, CDKN2A, PTEN, PIK3CA, RB1, germline mutations, DNA repair deficiency, gene fusion, immune microenvironment, tumor transcriptome, precision oncology
MeSH terms
Exome Sequencing, Adult, DNA Repair, Female, Genetics, Medical, Humans, Male, Neoplasm Metastasis, Tumor Suppressor Protein p53, Germ-Line Mutation, Cyclin-Dependent Kinase Inhibitor p16, Genomics, Ubiquitin-Protein Ligases, Cyclin-Dependent Kinase Inhibitor p18, PTEN Phosphohydrolase, Retinoblastoma Binding Proteins, Class I Phosphatidylinositol 3-Kinases, Tumor Microenvironment, Transcriptome

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