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Cancer Cell. 2016 May 9;29(5):723-736. doi: 10.1016/j.ccell.2016.04.002.

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.

Collaborators (226)

Zheng S, Verhaak RGW, Giordano TJ, Hammer GD, Cherniack AD, Dewal N, Moffitt RA, Danilova L, Murray BA, Lerario AM, Else T, Knijnenburg TA, Ciriello G, Kim S, Assié G, Morozova O, Akbani R, Shih J, Hoadley KA, Choueiri TK, Waldmann J, Mete O, Robertson AG, Wu HT, Raphael BJ, Meyerson M, Demeure MJ, Beuschlein F, Gill AJ, Sidhu SB, Almeida M, Barisson Fragoso MC, Cope LM, Kebebew E, Habra MA, Whitsett TG, Bussey KJ, Rainey WE, Asa SL, Bertherat J, Fassnacht M, Wheeler DA, Benz C, Ally A, Balasundaram M, Bowlby R, Brooks D, Butterfield YSN, Carlsen R, Dhalla N, Guin R, Holt RA, Jones SJM, Kasaian K, Lee D, Li HI, Lim L, Ma Y, Marra MA, Mayo M, Moore RA, Mungall AJ, Mungall K, Sadeghi S, Schein JE, Sipahimalani P, Tam A, Thiessen N, Park PJ, Kroiss M, Gao J, Sander C, Schultz N, Jones CD, Kucherlapati R, Mieczkowski PA, Parker JS, Perou CM, Tan D, Veluvolu U, Wilkerson MD, Hayes DN, Ladanyi M, Quinkler M, Auman JT, Latronico AC, Mendonca BB, Sibony M, Sanborn Z, Bellair M, Buhay C, Covington K, Dahdouli M, Dinh H, Doddapaneni H, Downs B, Drummond J, Gibbs R, Hale W, Han Y, Hawes A, Hu J, Kakkar N, Kalra D, Khan Z, Kovar C, Lee S, Lewis L, Morgan M, Morton D, Muzny D, Santibanez J, Xi L, Dousset B, Groussin L, Libé R, Chin L, Reynolds S, Shmulevich I, Chudamani S, Liu J, Lolla L, Wu Y, Yeh JJ, Balu S, Bodenheimer T, Hoyle AP, Jefferys SR, Meng S, Mose LE, Shi Y, Simons JV, Soloway MG, Wu J, Zhang W, Mills Shaw KR, Demchok JA, Felau I, Sheth M, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang JJ, Davidsen T, Crawford C, Hutter CM, Sofia HJ, Roach J, Bshara W, Gaudioso C, Morrison C, Soon P, Alonso S, Baboud J, Pihl T, Raman R, Sun Q, Wan Y, Naresh R, Arachchi H, Beroukhim R, Carter SL, Cho J, Frazer S, Gabriel SB, Getz G, Heiman DI, Kim J, Lawrence MS, Lin P, Noble MS, Saksena G, Schumacher SE, Sougnez C, Voet D, Zhang H, Bowen J, Coppens S, Gastier-Foster JM, Gerken M, Helsel C, Leraas KM, Lichtenberg TM, Ramirez NC, Wise L, Zmuda E, Baylin S, Herman JG, LoBello J, Watanabe A, Haussler D, Radenbaugh A, Rao A, Zhu J, Bartsch DK, Sbiera S, Allolio B, Deutschbein T, Ronchi C, Raymond VM, Vinco M, Shao L, Amble L, Bootwalla MS, Lai PH, Van Den Berg DJ, Weisenberger DJ, Robinson B, Ju Z, Kim H, Ling S, Liu W, Lu Y, Mills GB, Sircar K, Wang Q, Yoshihara K, Laird PW, Fan Y, Wang W, Shinbrot E, Reincke M, Weinstein JN, Meier S, Defreitas T.

Author information

1
Departments of Genomic Medicine, Bioinformatics, and Computational Biology, 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; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
3
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
4
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
5
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA.
6
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; Departments of Cell & Developmental Biology, Pathology, Molecular & Integrative Physiology, Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
7
Departments of Cell & Developmental Biology, Pathology, Molecular & Integrative Physiology, Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
8
Institute for Systems Biology, Seattle, WA 98109, USA.
9
Department of Computational Biology, University of Lausanne, Rue du Bugnon 27, 1005 Lausanne, Switzerland; Computational Biology Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
10
Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
11
Inserm U1016, CNRS UMR 8104, Institut Cochin, 75014 Paris, France; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France; Department of Endocrinology, Referral Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014 Paris, France; European Network for the Study of Adrenal Tumors, 75014 Paris, France.
12
University of California Santa Cruz Genomics Institute, University California Santa Cruz, Santa Cruz, CA 95064, USA.
13
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
14
European Network for the Study of Adrenal Tumors, 75014 Paris, France; Department of Visceral, Thoracic and Vascular Surgery, University Hospital Giessen and Marburg, Campus Marburg, General Surgery, Endocrine Center, 34501 Marburg, Germany.
15
Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto, ON M5G 2C4, Canada.
16
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
17
Department of Computer Science, Brown University, Providence, RI 02906, USA.
18
Departments of Cell & Developmental Biology, Pathology, Molecular & Integrative Physiology, Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
19
The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Pathology, Harvard Medical School, Boston, MA 02215, USA.
20
European Network for the Study of Adrenal Tumors, 75014 Paris, France; Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, 80336 Munich, Germany.
21
Cancer Diagnosis and Pathology Group and Cancer Genetics Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2006, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
22
Cancer Diagnosis and Pathology Group and Cancer Genetics Laboratory, Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2006, Australia; Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
23
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; Instituto do Câncer do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-900, Brazil.
24
Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
25
Translational Genomics Research Institute, Phoenix, AZ 85004, USA; NantOmics, LLC, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5001, USA.
26
European Network for the Study of Adrenal Tumors, 75014 Paris, France; Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Cancer Center Mainfranken, University of Würzburg, 97080 Würzburg, Germany.
27
Departments of Cell & Developmental Biology, Pathology, Molecular & Integrative Physiology, Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: giordano@med.umich.edu.
28
Departments of Genomic Medicine, Bioinformatics, and Computational Biology, Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rverhaak@mdanderson.org.

Abstract

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.

PMID:
27165744
PMCID:
PMC4864952
DOI:
10.1016/j.ccell.2016.04.002
[Indexed for MEDLINE]
Free PMC Article

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