Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Siyuan Zheng, Andrew D. Cherniack, Ninad Dewal, Richard A. Moffitt, Liudmila V Danilova, Bradley A. Murray, Antonio M. Lerario, Tobias Else, Theo A. Knijnenburg, Giovanni Ciriello, Seungchan Kim, Guillaume Assie, Olena Morozova, Rehan Akbani, Juliann Shih, Katherine A. Hoadley, Toni K. Choueiri, Jens Waldmann, Ozgur Mete, A. Gordon RobertsonHsin Ta Wu, Benjamin J. Raphael, Lina Shao, Matthew Meyerson, Michael J. Demeure, Felix Beuschlein, Anthony J. Gill, Stan B. Sidhu, Madson Q. Almeida, Maria C B V Fragoso, Leslie Cope, Electron Kebebew, Mouhammed A. Habra, Timothy G. Whitsett, Kimberly J. Bussey, William E. Rainey, Sylvia L. Asa, Jérôme Bertherat, Martin Fassnacht, David A. Wheeler, Gary D. Hammer, Thomas J. Giordano, Stephen B Baylin

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)723-736
Number of pages14
JournalCancer Cell
Volume29
Issue number5
DOIs
StatePublished - May 9 2016

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Adrenocortical Carcinoma
Genome
DNA
Telomere
DNA Methylation
Genes
Disease Progression
Cell Cycle

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma. / Zheng, Siyuan; Cherniack, Andrew D.; Dewal, Ninad; Moffitt, Richard A.; Danilova, Liudmila V; Murray, Bradley A.; Lerario, Antonio M.; Else, Tobias; Knijnenburg, Theo A.; Ciriello, Giovanni; Kim, Seungchan; Assie, Guillaume; Morozova, Olena; Akbani, Rehan; Shih, Juliann; Hoadley, Katherine A.; Choueiri, Toni K.; Waldmann, Jens; Mete, Ozgur; Robertson, A. Gordon; Wu, Hsin Ta; Raphael, Benjamin J.; Shao, Lina; Meyerson, Matthew; Demeure, Michael J.; Beuschlein, Felix; Gill, Anthony J.; Sidhu, Stan B.; Almeida, Madson Q.; Fragoso, Maria C B V; Cope, Leslie; Kebebew, Electron; Habra, Mouhammed A.; Whitsett, Timothy G.; Bussey, Kimberly J.; Rainey, William E.; Asa, Sylvia L.; Bertherat, Jérôme; Fassnacht, Martin; Wheeler, David A.; Hammer, Gary D.; Giordano, Thomas J.; Baylin, Stephen B.

In: Cancer Cell, Vol. 29, No. 5, 09.05.2016, p. 723-736.

Research output: Contribution to journalArticle

Zheng, S, Cherniack, AD, Dewal, N, Moffitt, RA, Danilova, LV, Murray, BA, Lerario, AM, Else, T, Knijnenburg, TA, Ciriello, G, Kim, S, Assie, G, Morozova, O, Akbani, R, Shih, J, Hoadley, KA, Choueiri, TK, Waldmann, J, Mete, O, Robertson, AG, Wu, HT, Raphael, BJ, Shao, L, Meyerson, M, Demeure, MJ, Beuschlein, F, Gill, AJ, Sidhu, SB, Almeida, MQ, Fragoso, MCBV, Cope, L, Kebebew, E, Habra, MA, Whitsett, TG, Bussey, KJ, Rainey, WE, Asa, SL, Bertherat, J, Fassnacht, M, Wheeler, DA, Hammer, GD, Giordano, TJ & Baylin, SB 2016, 'Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma', Cancer Cell, vol. 29, no. 5, pp. 723-736. https://doi.org/10.1016/j.ccell.2016.04.002
Zheng, Siyuan ; Cherniack, Andrew D. ; Dewal, Ninad ; Moffitt, Richard A. ; Danilova, Liudmila V ; Murray, Bradley A. ; Lerario, Antonio M. ; Else, Tobias ; Knijnenburg, Theo A. ; Ciriello, Giovanni ; Kim, Seungchan ; Assie, Guillaume ; Morozova, Olena ; Akbani, Rehan ; Shih, Juliann ; Hoadley, Katherine A. ; Choueiri, Toni K. ; Waldmann, Jens ; Mete, Ozgur ; Robertson, A. Gordon ; Wu, Hsin Ta ; Raphael, Benjamin J. ; Shao, Lina ; Meyerson, Matthew ; Demeure, Michael J. ; Beuschlein, Felix ; Gill, Anthony J. ; Sidhu, Stan B. ; Almeida, Madson Q. ; Fragoso, Maria C B V ; Cope, Leslie ; Kebebew, Electron ; Habra, Mouhammed A. ; Whitsett, Timothy G. ; Bussey, Kimberly J. ; Rainey, William E. ; Asa, Sylvia L. ; Bertherat, Jérôme ; Fassnacht, Martin ; Wheeler, David A. ; Hammer, Gary D. ; Giordano, Thomas J. ; Baylin, Stephen B. / Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma. In: Cancer Cell. 2016 ; Vol. 29, No. 5. pp. 723-736.
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AU - Zheng, Siyuan

AU - Cherniack, Andrew D.

AU - Dewal, Ninad

AU - Moffitt, Richard A.

AU - Danilova, Liudmila V

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

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 - Baylin, Stephen B

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