Comprehensive pan-genomic characterization of adrenocortical carcinoma

The Cancer Genome Atlas Research Network

doi:10.1016/j.ccell.2016.04.002

Comprehensive pan-genomic characterization of adrenocortical carcinoma

The Cancer Genome Atlas Research Network

Department of Pharmacy

University of Texas MD Anderson Cancer Center
Broad Institute
Harvard University
Baylor College of Medicine
University of North Carolina at Chapel Hill
Johns Hopkins University
Intellia Therapeutics
Universidade de São Paulo
University of Michigan, Ann Arbor
Institute for Systems Biology
University of Lausanne
Memorial Sloan-Kettering Cancer Center
Translational Genomics Research Institute
Institut Cochin
Université Paris Cité
European Network for the Study of Adrenal Tumors
University of California at Santa Cruz
Brigham and Women’s Hospital
University of Marburg
University Health Network
Provincial Health Services Authority
Brown University
Ashion Analytics
Ludwig Maximilian University of Munich
University of Sydney
Royal North Shore Hospital
National Institutes of Health
Arizona State University
University of Würzburg

Research output: Contribution to journal › Article › peer-review

489 Scopus citations

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, suggestingWGDis 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.

Original language	English
Pages (from-to)	723-736
Number of pages	14
Journal	Cancer Cell
Volume	29
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2016.04.002
State	Published - 9 May 2016

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10.1016/j.ccell.2016.04.002

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@article{2516a4c4c2bd4569a0c1ecb18ed05d3a,

title = "Comprehensive pan-genomic characterization of adrenocortical carcinoma",

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, suggestingWGDis 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.",

author = "\{The Cancer Genome Atlas Research Network\} and Siyuan Zheng and Cherniack, \{Andrew D.\} and Ninad Dewal and Moffitt, \{Richard A.\} and Ludmila Danilova and Murray, \{Bradley A.\} and Lerario, \{Antonio M.\} and Tobias Else and Knijnenburg, \{Theo A.\} and Giovanni Ciriello and Seungchan Kim and Guillaume Assie and Olena Morozova and Rehan Akbani and Juliann Shih and Hoadley, \{Katherine A.\} and Choueiri, \{Toni K.\} and Jens Waldmann and Ozgur Mete and Robertson, \{A. Gordon\} and Wu, \{Hsin Ta\} and Raphael, \{Benjamin J.\} and Lina Shao and Matthew Meyerson and Demeure, \{Michael J.\} and Felix Beuschlein and Gill, \{Anthony J.\} and Sidhu, \{Stan B.\} and Almeida, \{Madson Q.\} and Fragoso, \{Maria C.B.V.\} and Cope, \{Leslie M.\} and Electron Kebebew and Habra, \{Mouhammed A.\} and Whitsett, \{Timothy G.\} and Bussey, \{Kimberly J.\} and Rainey, \{William E.\} and Asa, \{Sylvia L.\} and J{\'e}r{\^o}me Bertherat and Martin Fassnacht and Wheeler, \{David A.\} and Hammer, \{Gary D.\} and Giordano, \{Thomas J.\} and Verhaak, \{Roel G.W.\} and Christopher Benz and Adrian Ally and Miruna Balasundaram and Reanne Bowlby and Denise Brooks and Butterfield, \{Yaron S.N.\} and Hoon Kim",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = may,

day = "9",

doi = "10.1016/j.ccell.2016.04.002",

language = "English",

volume = "29",

pages = "723--736",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Comprehensive pan-genomic characterization of adrenocortical carcinoma

AU - The Cancer Genome Atlas Research Network

AU - Zheng, Siyuan

AU - Cherniack, Andrew D.

AU - Dewal, Ninad

AU - Moffitt, Richard A.

AU - Danilova, Ludmila

AU - Murray, Bradley A.

AU - Lerario, Antonio M.

AU - Else, Tobias

AU - Knijnenburg, Theo A.

AU - Ciriello, Giovanni

AU - Kim, Seungchan

AU - Assie, Guillaume

AU - Morozova, Olena

AU - Akbani, Rehan

AU - Shih, Juliann

AU - Hoadley, Katherine A.

AU - Choueiri, Toni K.

AU - Waldmann, Jens

AU - Mete, Ozgur

AU - Robertson, A. Gordon

AU - Wu, Hsin Ta

AU - Raphael, Benjamin J.

AU - Shao, Lina

AU - Meyerson, Matthew

AU - Demeure, Michael J.

AU - Beuschlein, Felix

AU - Gill, Anthony J.

AU - Sidhu, Stan B.

AU - Almeida, Madson Q.

AU - Fragoso, Maria C.B.V.

AU - Cope, Leslie M.

AU - Kebebew, Electron

AU - Habra, Mouhammed A.

AU - Whitsett, Timothy G.

AU - Bussey, Kimberly J.

AU - Rainey, William E.

AU - Asa, Sylvia L.

AU - Bertherat, Jérôme

AU - Fassnacht, Martin

AU - Wheeler, David A.

AU - Hammer, Gary D.

AU - Giordano, Thomas J.

AU - Verhaak, Roel G.W.

AU - Benz, Christopher

AU - Ally, Adrian

AU - Balasundaram, Miruna

AU - Bowlby, Reanne

AU - Brooks, Denise

AU - Butterfield, Yaron S.N.

AU - Kim, Hoon

PY - 2016/5/9

Y1 - 2016/5/9

N2 - 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, suggestingWGDis 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.

AB - 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, suggestingWGDis 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.

UR - https://www.scopus.com/pages/publications/84975223445

U2 - 10.1016/j.ccell.2016.04.002

DO - 10.1016/j.ccell.2016.04.002

M3 - Article

C2 - 27165744

AN - SCOPUS:84975223445

SN - 1535-6108

VL - 29

SP - 723

EP - 736

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

Comprehensive pan-genomic characterization of adrenocortical carcinoma

Abstract

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