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Integrative clinical genomics of metastatic cancer

Author

Listed:
  • Dan R. Robinson

    (Michigan Center for Translational Pathology, University of Michigan
    University of Michigan)

  • Yi-Mi Wu

    (Michigan Center for Translational Pathology, University of Michigan
    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
    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
    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
    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
    University of Michigan)

  • Moshe Talpaz

    (Comprehensive Cancer Center, University of Michigan)

  • Marcin Cieślik

    (Michigan Center for Translational Pathology, University of Michigan
    University of Michigan)

  • Arul M. Chinnaiyan

    (Michigan Center for Translational Pathology, University of Michigan
    University of Michigan
    Comprehensive Cancer Center, University of Michigan
    University of Michigan)

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.

Suggested Citation

  • 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 , 2017. "Integrative clinical genomics of metastatic cancer," Nature, Nature, vol. 548(7667), pages 297-303, August.
    • Handle: RePEc:nat:nature:v:548:y:2017:i:7667:d:10.1038_nature23306
    DOI: 10.1038/nature23306
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    Cited by:

    1. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. W. Dean Pontius & Ellen S. Hong & Zachary J. Faber & Jeremy Gray & Craig D. Peacock & Ian Bayles & Katreya Lovrenert & Diana H. Chin & Berkley E. Gryder & Cynthia F. Bartels & Peter C. Scacheri, 2023. "Temporal chromatin accessibility changes define transcriptional states essential for osteosarcoma metastasis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Huiqiang Cai & Bin Zhang & Johanne Ahrenfeldt & Justin V. Joseph & Maria Riedel & Zongliang Gao & Sofie K. Thomsen & Ditte S. Christensen & Rasmus O. Bak & Henrik Hager & Mikkel H. Vendelbo & Xin Gao , 2024. "CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Biaobin Jiang & Quanhua Mu & Fufang Qiu & Xuefeng Li & Weiqi Xu & Jun Yu & Weilun Fu & Yong Cao & Jiguang Wang, 2021. "Machine learning of genomic features in organotropic metastases stratifies progression risk of primary tumors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    6. Brian D. Lehmann & Antonio Colaprico & Tiago C. Silva & Jianjiao Chen & Hanbing An & Yuguang Ban & Hanchen Huang & Lily Wang & Jamaal L. James & Justin M. Balko & Paula I. Gonzalez-Ericsson & Melinda , 2021. "Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    7. Josh N. Vo & Yi-Mi Wu & Jeanmarie Mishler & Sarah Hall & Rahul Mannan & Lisha Wang & Yu Ning & Jin Zhou & Alexander C. Hopkins & James C. Estill & Wallace K. B. Chan & Jennifer Yesil & Xuhong Cao & Ar, 2022. "The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    8. Amanda Fitzpatrick & Marjan Iravani & Adam Mills & David Vicente & Thanussuyah Alaguthurai & Ioannis Roxanis & Nicholas C. Turner & Syed Haider & Andrew N. J. Tutt & Clare M. Isacke, 2023. "Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Marco Bolis & Daniela Bossi & Arianna Vallerga & Valentina Ceserani & Manuela Cavalli & Daniela Impellizzieri & Laura Di Rito & Eugenio Zoni & Simone Mosole & Angela Rita Elia & Andrea Rinaldi & Ricar, 2021. "Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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