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      Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

      research-article
      1 , 2 , 3 , 4 , 5 , 6 , 2 , 3 , 4 , 7 , 8 , 9 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 1 , 2 , 3 , 5 , 2 , 19 , 17 , 20 , 21 , 22 , 23 , 23 , 8 , 2 , 3 , 24 , 13 , 35, 17 , 25 , 26 , 27 , 26 , 28 , 7 , 29 , 7 , 29 , 6 , 30 , 1 , 13 , 13 , 31 , 8 , 9 , 21 , 14 , 15 , 16 , 17 , 17 , 32 , 33 , 4 , The Cancer Genome Atlas Research Network, 8 , 9 , 36, 8 , 9 , 36, 1 , 36
      Cancer cell

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          SUMMARY

          We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy number analysis revealed frequent occurrence of massive DNA loss followed by whole genome doubling (WGD) which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68 CpG probe DNA methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.

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          Zheng et al. perform comprehensive genomic characterization of 91 cases of adrenocortical carcinoma (ACC). This analysis expands the list of driver genes in ACC, reveals whole genome doubling as a hallmark of ACC progression, and identifies three ACC subtypes with distinct clinical outcome.

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          Author and article information

          Journal
          101130617
          29778
          Cancer Cell
          Cancer Cell
          Cancer cell
          1535-6108
          1878-3686
          14 April 2016
          9 May 2016
          09 May 2017
          : 29
          : 5
          : 723-736
          Affiliations
          [1 ]Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
          [2 ]The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
          [3 ]Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
          [4 ]Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA
          [5 ]Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
          [6 ]The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA
          [7 ]Unidade de Suprarrenal, Laboratório de Hormônios e Genética Molecular LIM42, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-900, Brazil
          [8 ]Department of Cell & Developmental Biology, Department of Pathology, Department of Molecular & Integrative Physiology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
          [9 ]University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
          [10 ]Institute for Systems Biology, Seattle, WA 98109, USA
          [11 ]Department of Computational Biology, University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland
          [12 ]Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
          [13 ]Translational Genomics Research Institute, Phoenix, AZ 85004, USA
          [14 ]Inserm U1016, CNRS UMR 8104, Institut Cochin, 75014 Paris, France
          [15 ]Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France
          [16 ]Department of Endocrinology, Referral Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014 Paris, France
          [17 ]European Network for the Study of Adrenal Tumors
          [18 ]University of California Santa Cruz Genomics Institute, University California Santa Cruz, Santa Cruz, CA 95064, USA
          [19 ]Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
          [20 ]Department of Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg, Campus Marburg, General Surgery, Endocrine Center, 34501 Marburg, Germany
          [21 ]Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto, Ontario M5G 2C4, Canada
          [22 ]Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada
          [23 ]Department of Computer Science, Brown University, Providence, RI 02906, USA
          [24 ]Department of Pathology, Harvard Medical School, Boston, Massachusetts 02215, USA
          [25 ]Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, D-80336 Munich, Germany
          [26 ]University of Sydney, Australia NSW 2006, Australia
          [27 ]Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
          [28 ]Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
          [29 ]Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-900, Brazil
          [30 ]Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda 20892, MD, USA
          [31 ]NantOmics, LLC, The Biodesign Institute, Arizona State University, Tempe, AZ, 85287-5001, USA
          [32 ]Department of Internal Medicine I, Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany
          [33 ]Comprehensive Cancer Center Mainfranken, University of Würzburg, 97080 Würzburg, Germany
          Author notes
          [* ]Correspondence: T. J. G ( giordano@ 123456med.umich.edu ), R. G.W. V ( rverhaak@ 123456mdanderson.org )
          [34]

          Present address: Intellia Therapeutics, Cambridge, MA 02139, USA

          [35]

          Present address: Ashion Analytics, Phoenix, AZ 85004

          [36]

          Co-senior author

          Article
          PMC4864952 PMC4864952 4864952 nihpa777121
          10.1016/j.ccell.2016.04.002
          4864952
          27165744
          d8120af8-94fd-470a-87f3-d83e94c294f0
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