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ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma

Author

Listed:
  • Mamunur Rashid

    (Wellcome Trust Sanger Institute)

  • Michiel van der Horst

    (Maasstad Hospital)

  • Thomas Mentzel

    (Dermatopathologie Friedrichshafen)

  • Francesca Butera

    (Division of Cancer Biology. Institute of Cancer Research)

  • Ingrid Ferreira

    (Wellcome Trust Sanger Institute)

  • Alena Pance

    (Wellcome Trust Sanger Institute)

  • Arno Rütten

    (Dermatopathologie Friedrichshafen)

  • Bostjan Luzar

    (Medical Faculty University of Ljubljana)

  • Zlatko Marusic

    (University Hospital Center Zagreb)

  • Nicolas de Saint Aubain

    (Institut Jules Bordet)

  • Jennifer S. Ko

    (Cleveland Clinic)

  • Steven D. Billings

    (Cleveland Clinic)

  • Sofia Chen

    (Wellcome Trust Sanger Institute)

  • Marie Abi Daoud

    (University of Calgary)

  • James Hewinson

    (Wellcome Trust Sanger Institute)

  • Sandra Louzada

    (Wellcome Trust Sanger Institute)

  • Paul W. Harms

    (University of Michigan Medical School)

  • Guia Cerretelli

    (The University of Edinburgh, Institute of Genetics & Molecular Medicine)

  • Carla Daniela Robles-Espinoza

    (Wellcome Trust Sanger Institute
    Universidad Nacional Autónoma de México)

  • Rajiv M. Patel

    (University of Michigan Medical School)

  • Louise van der Weyden

    (Wellcome Trust Sanger Institute)

  • Chris Bakal

    (Division of Cancer Biology. Institute of Cancer Research)

  • Jason L. Hornick

    (Harvard Medical School)

  • Mark J. Arends

    (The University of Edinburgh, Institute of Genetics & Molecular Medicine)

  • Thomas Brenn

    (University of Calgary
    The University of Edinburgh, Institute of Genetics & Molecular Medicine)

  • David J. Adams

    (Wellcome Trust Sanger Institute)

Abstract

Spiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation and potential for malignant transformation and aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma–spiradenoma hybrid tumors, and 24 low- and high-grade spiradenocarcinoma cases, together with morphologically benign precursor regions of these cancers. We reveal somatic or germline alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas. Notably, we find a recurrent missense mutation in the kinase domain of the ALPK1 gene in spiradenomas and spiradenocarcinomas, which is mutually exclusive from mutation of CYLD and can activate the NF-κB pathway in reporter assays. In addition, we show that high-grade spiradenocarcinomas carry loss-of-function TP53 mutations, while cylindromas may have disruptive mutations in DNMT3A. Thus, we reveal the genomic landscape of adnexal tumors and therapeutic targets.

Suggested Citation

  • Mamunur Rashid & Michiel van der Horst & Thomas Mentzel & Francesca Butera & Ingrid Ferreira & Alena Pance & Arno Rütten & Bostjan Luzar & Zlatko Marusic & Nicolas de Saint Aubain & Jennifer S. Ko & , 2019. "ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09979-0
    DOI: 10.1038/s41467-019-09979-0
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    Cited by:

    1. Yaodong Zhang & Zijian Ma & Changxian Li & Cheng Wang & Wangjie Jiang & Jiang Chang & Sheng Han & Zefa Lu & Zicheng Shao & Yirui Wang & Hongwei Wang & Chenyu Jiao & Dong Wang & Xiaofeng Wu & Hongbing , 2022. "The genomic landscape of cholangiocarcinoma reveals the disruption of post-transcriptional modifiers," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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