Genomic landscape of paediatric adrenocortical tumours

Emilia M. Pinto, Xiang Chen, John Easton, David Finkelstein, Zhifa Liu, Stanley Pounds, Carlos Rodriguez-Galindo, Troy C. Lund, Elaine R. Mardis, Richard K. Wilson, Kristy Boggs, Donald Yergeau, Jinjun Cheng, Heather L. Mulder, Jayanthi Manne, Jesse Jenkins, Maria J. Mastellaro, Bonald C. Figueiredo, Michael A. Dyer, Alberto Pappo, Jinghui Zhang (), James R. Downing, Raul C. Ribeiro () and Gerard P. Zambetti ()
Additional contact information
Emilia M. Pinto: St Jude Children’s Research Hospital
Xiang Chen: St Jude Children’s Research Hospital
John Easton: St Jude Children’s Research Hospital
David Finkelstein: St Jude Children’s Research Hospital
Zhifa Liu: St Jude Children’s Research Hospital
Stanley Pounds: St Jude Children’s Research Hospital
Carlos Rodriguez-Galindo: Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Harvard Medical School
Troy C. Lund: University of Minnesota Medical School
Elaine R. Mardis: The Genome Institute, Washington University School of Medicine
Richard K. Wilson: The Genome Institute, Washington University School of Medicine
Kristy Boggs: St Jude Children’s Research Hospital
Donald Yergeau: St Jude Children’s Research Hospital
Jinjun Cheng: St Jude Children’s Research Hospital
Heather L. Mulder: St Jude Children’s Research Hospital
Jayanthi Manne: St Jude Children’s Research Hospital
Jesse Jenkins: St Jude Children’s Research Hospital
Maria J. Mastellaro: Boldrini Children’s Research Hospital
Bonald C. Figueiredo: Instituto de Pesquisa Pelé Pequeno Príncipe
Michael A. Dyer: St Jude Children’s Research Hospital
Alberto Pappo: St Jude Children’s Research Hospital
Jinghui Zhang: St Jude Children’s Research Hospital
James R. Downing: St Jude Children’s Research Hospital
Raul C. Ribeiro: St Jude Children’s Research Hospital
Gerard P. Zambetti: St Jude Children’s Research Hospital

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract Paediatric adrenocortical carcinoma is a rare malignancy with poor prognosis. Here we analyse 37 adrenocortical tumours (ACTs) by whole-genome, whole-exome and/or transcriptome sequencing. Most cases (91%) show loss of heterozygosity (LOH) of chromosome 11p, with uniform selection against the maternal chromosome. IGF2 on chromosome 11p is overexpressed in 100% of the tumours. TP53 mutations and chromosome 17 LOH with selection against wild-type TP53 are observed in 28 ACTs (76%). Chromosomes 11p and 17 undergo copy-neutral LOH early during tumorigenesis, suggesting tumour-driver events. Additional genetic alterations include recurrent somatic mutations in ATRX and CTNNB1 and integration of human herpesvirus-6 in chromosome 11p. A dismal outcome is predicted by concomitant TP53 and ATRX mutations and associated genomic abnormalities, including massive structural variations and frequent background mutations. Collectively, these findings demonstrate the nature, timing and potential prognostic significance of key genetic alterations in paediatric ACT and outline a hypothetical model of paediatric adrenocortical tumorigenesis.

Date: 2015
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DOI: 10.1038/ncomms7302

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