Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
Authors: Matthew D Wilkerson
Katherine A Hoadley
Saianand Balu
Matthias Kroiss
Margi Sheth
Yiling Lu
D Neil Hayes
Cancer Genome Atlas Research Network
Madson Almeida
Mouhammed Amir Habra
Qianghu Wang
Christian Buhay
Andrew J Mungall
Julien Baboud
Jen Jen Yeh
Andrew D Cherniack
Lisa Wise
Rebecca Carlsen
Rohini Raman
Patsy Soon
Felix Beuschlein
Jaegil Kim
Lora Lewis
Moiz S Bootwalla
Wenyi Wang
Wenbin Liu
Guillaume Assi√©
Jeffrey Roach
Ozgur Mete
J Todd Auman
Piotr A Mieczkowski
David A Wheeler
Reanne Bowlby
Silviu Sbiera
Anthony J Gill
Tom Bodenheimer
Ludmila Danilova
Umadevi Veluvolu
Peter J Park
Scott L Carter
Joel S Parker
Donna Muzny
Robert A Holt
Jingchun Zhu
Juliann Shih
Alicia Hawes
Sandy Lee
Jianhong Hu
Wiam Bshara
Michael S Noble
Kenna R Mills Shaw
John A Demchok
Stephen Baylin
Kosuke Yoshihara
Hailei Zhang
Michael Mayo
Rashi Naresh
Kanishka Sircar
Janae V Simons
Lynette Lim
Angela Tam
Marco A Marra
Rameen Beroukhim
Arjun Rao
Sam Meier
Tara M Lichtenberg
Phillip H Lai
Scott Frazer
Jennifer Drummond
Yussanne Ma
David J Van Den Berg
Jens Waldmann
Heidi J Sofia
Cristina Ronchi
Siyuan Zheng
Rossella Lib√©
Toni K Choueiri
Nina Thiessen
Yunhu Wan
Margaret Morgan
Adrian Ally
Carrie Sougnez
Jianjiong Gao
Janine LoBello
Junyuan Wu
Yaron S N Butterfield
Madson Q Almeida
Martin Fassnacht
Jean C Zenklusen
Sudha Chudamani
Erik Zmuda
Laxmi Lolla
Ziad Khan
Christine Kovar
Mark Gerken
Ilya Shmulevich
Qiang Sun
Jay Bowen
Jia Liu
Matthew Meyerson
Leslie M Cope
Berenice B Mendonca
Tobias Else
Chris Sander
Lina Shao
Darlene Lee
Zhining Wang
Mouhammed A Habra
Theo A Knijnenburg
Brittany Downs
Mathilde Sibony
Peter W Laird
Wei Zhang
Benjamin J Raphael
Lionel Groussin
J√©r√¥me Bertherat
Payal Sipahimalani
Mahmoud Dahdouli
Marc Ladanyi
Kyle Covington
Maria C B V Fragoso
Donna Morton
Shaowu Meng
Electron Kebebew
Liming Yang
Stan B Sidhu
Olena Morozova
Carl Morrison
Corbin D Jones
Charles M Perou
Nilsa C Ramirez
Alan P Hoyle
Richard A Moore
Donghui Tan
Matthew G Soloway
Jireh Santibanez
Hsin-Tu Wu
Timothy Defreitas
Aprill Watanabe
Daniel J Weisenberger
Harindra Arachchi
Katayoon Kasaian
Amie Radenbaugh
Michelle Bellair
Jiashan Julia Zhang
Steven E Schumacher
Ninad Dewal
Gary D Hammer
Noreen Dhalla
Shiyun Ling
Nipun Kakkar
Ranabir Guin
Liu Xi
William E Rainey
Catherine Crawford
Karen Mungall
Martin Reincke
Sheila Reynolds
Pei Lin
Lisle E Mose
Kristen M Leraas
Thomas J Giordano
Shelley Alonso
Rehan Akbani
Gordon Saksena
Marcus Quinkler
Bruce Robinson
Raju Kucherlapati
Ina Felau
Nikolaus Schultz
Bradley A Murray
Miruna Balasundaram
Guillaume Assie
Victoria M Raymond
Ye Wu
Zack Sanborn
David Haussler
Antonio M Lerario
Walker Hale
Gad Getz
Michael J Demeure
Linda Amble
Stuart R Jefferys
Zhenlin Ju
Lynda Chin
Roel G W Verhaak
Steven J M Jones
Yi Han
Sylvia L Asa
Haiyan I Li
Jacqueline E Schein
Roy Tarnuzzer
John N Weinstein
Doug Voet
A Gordon Robertson
Maria Candida Barisson Fragoso
Julie M Gastier-Foster
Christopher Benz
Richard Gibbs
Michelle Vinco
Detlef K Bartsch
Stacey B Gabriel
Bruno Allolio
David I Heiman
Tanja Davidsen
Harsha Doddapaneni
James G Herman
Bertrand Dousset
Huyen Dinh
Kimberly J Bussey
Divya Kalra
Ana Claudia Latronico
Carmen Helsel
Sara Sadeghi
Carolyn M Hutter
Giovanni Ciriello
Todd Pihl
Timo Deutschbein
Gordon B Mills
Yu Fan
Sara Coppens
Carmelo Gaudioso
Eve Shinbrot
Timothy G Whitsett
Yan Shi
Hoon Kim
Seungchan Kim
Juok Cho
Denise Brooks
Hsin-Ta Wu
Richard A Moffitt
Michael S Lawrence
Journal: Cancer cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Adrenocortical carcinoma; Genomic characterization; Driver genes; DNA copy-number analysis; Whole-genome doubling
Affiliations: 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., 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., Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA., Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21287, USA., Unidade de Suprarrenal, Laborat√≥rio de Horm√¥nios e Gen√©tica Molecular LIM42, Servi√ßo de Endocrinologia e Metabologia, Hospital das Cl√≠nicas, Faculdade de Medicina da Universidade de S√£o Paulo, S√£o 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., 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., Institute for Systems Biology, Seattle, WA 98109, USA., 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., Translational Genomics Research Institute, Phoenix, AZ 85004, USA., Inserm U1016, CNRS UMR 8104, Institut Cochin, 75014 Paris, France; Facult√© de M√©decine Paris Descartes, Universit√© Paris Descartes, Sorbonne Paris Cit√©, 75006 Paris, France; Department of Endocrinology, Referral Center for Rare Adrenal Diseases, Assistance Publique H√¥pitaux de Paris, H√¥pital Cochin, 75014 Paris, France; European Network for the Study of Adrenal Tumors, 75014 Paris, France., University of California Santa Cruz Genomics Institute, University California Santa Cruz, Santa Cruz, CA 95064, USA., 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., 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., Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto, ON M5G 2C4, Canada., Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada., Department of Computer Science, Brown University, Providence, RI 02906, USA., Departments of Cell & Developmental Biology, Pathology, Molecular & Integrative Physiology, Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA., 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., European Network for the Study of Adrenal Tumors, 75014 Paris, France; Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universit√§t M√ºnchen, 80336 Munich, Germany., 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., 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., Unidade de Suprarrenal, Laborat√≥rio de Horm√¥nios e Gen√©tica Molecular LIM42, Servi√ßo de Endocrinologia e Metabologia, Hospital das Cl√≠nicas, Faculdade de Medicina da Universidade de S√£o Paulo, S√£o Paulo 05403-900, Brazil; Instituto do C√¢ncer do Estado de S√£o Paulo (ICESP), Faculdade de Medicina da Universidade de S√£o Paulo, S√£o Paulo 05403-900, Brazil., Endocrine Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Translational Genomics Research Institute, Phoenix, AZ 85004, USA; NantOmics, LLC, The Biodesign Institute, Arizona State University, Tempe, AZ 85287-5001, USA., European Network for the Study of Adrenal Tumors, 75014 Paris, France; Endocrine and Diabetes Unit, Department of Internal Medicine I, University Hospital W√ºrzburg, 97080 W√ºrzburg, Germany; Comprehensive Cancer Center Mainfranken, University of W√ºrzburg, 97080 W√ºrzburg, Germany., 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: ., 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: ., Departments of Genomic Medicine, Bioinformatics, and Computational Biology, Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, U

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. 

Retracted: No

PubPeer comments:
 This is not work from the Gary Stacey lab ,