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Genomic landscape of paediatric adrenocortical tumours

Author

Listed:
  • 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
    Washington University School of Medicine
    Washington University School of Medicine)

  • Richard K. Wilson

    (The Genome Institute, Washington University School of Medicine
    Washington University School of Medicine
    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)

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.

Suggested Citation

  • 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 Yer, 2015. "Genomic landscape of paediatric adrenocortical tumours," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7302
    DOI: 10.1038/ncomms7302
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    Cited by:

    1. Nicholas Light & Mehdi Layeghifard & Ayush Attery & Vallijah Subasri & Matthew Zatzman & Nathaniel D. Anderson & Rupal Hatkar & Sasha Blay & David Chen & Ana Novokmet & Fabio Fuligni & James Tran & Ri, 2023. "Germline TP53 mutations undergo copy number gain years prior to tumor diagnosis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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