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 PappoJinghui Zhang, James R. Downing, Raul C. Ribeiro, Gerard P. Zambetti

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


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.

Original languageEnglish (US)
Article number6302
JournalNature communications
StatePublished - Mar 2015

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© 2015 Macmillan Publishers Limited.


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