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Research Article| Volume 45, ISSUE 2, P116-126, February 2013

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Tumours associated with BAP1 mutations

  • Rajmohan Murali
    Correspondence
    Address for correspondence: Department of Pathology, and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, Box 20, 1275 York Avenue, New York, NY 10065, USA
    Affiliations
    Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, USA

    Department of Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USA
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  • Thomas Wiesner
    Affiliations
    Department of Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USA

    Department of Dermatology, Medical University ofGraz, Austria, Australia
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  • Richard A. Scolyer
    Affiliations
    Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Australia

    Department of Discipline of Pathology, Sydney Medical School, The University of Sydney, Camperdown, Australia

    Melanoma Institute Australia, North Sydney, NSW, Australia
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DOI:https://doi.org/10.1097/PAT.0b013e32835d0efb
Tumours associated with BAP1 mutations
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      Summary

      BAP1 (BRCA1-Associated Protein 1) was initially identified as a protein that binds to BRCA1. BAP1 is a tumour suppressor that is believed to mediate its effects through chromatin modulation, transcriptional regulation, and possibly via the ubiquitin-proteasome system and the DNA damage response pathway. Germline mutations of BAP1 confer increased susceptibility for the developmentofseveral tumours, including uveal melanoma, epithelioid atypical Spitz tumours, cutaneous melanoma, and mesothelioma. However, the complete tumour spectrum associated with germline BAP1 mutations is not yet known. Somatic BAP1 mutations are seen in cutaneous melanocytic tumours (epithelioid atypical Spitz tumours and melanoma), uveal melanoma, mesothelioma, clear cell renal cell carcinoma, and other tumours. Here, we review the current state of knowledge about the functional roles of BAP1, and summarise data on tumours associated with BAP1 mutations. Awareness of these tumours will help pathologists and clinicians to identify patients with a high likelihood of harbouring germline or somatic BAP1 mutations. We recommend that pathologists consider testing for BAP1 mutations in epithelioid atypical Spitz tumours and uveal melanomas, or when other BAP1-associated tumours occur in individual patients. Tumour tissues may be screened for BAP1 mutations/loss/inactivation by immunohistochemistry (IHC) (demonstrated by loss of nuclear staining in tumour cells). Confirmatory sequencing may be considered in tumours that exhibit BAP1 loss by IHC and in those with equivocal IHC results. If a BAP1 mutation is confirmed in a tumour, the patient’s treating physician should be informed of the possibility of a BAP1 germline mutation, so they can consider whether genetic counselling and further testing of the patient and investigation of their family is appropriate. Recognition and evaluation of larger numbers of BAP1-associated tumours will also be necessary to facilitate identification of additional distinct clinico-pathological characteristics or other genotype-phenotype correlations that may have prognostic and management implications.

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      Article info

      Publication history

      Accepted: November 20, 2012
      Received in revised form: November 16, 2012
      Received: October 5, 2012

      Identification

      DOI: https://doi.org/10.1097/PAT.0b013e32835d0efb

      Copyright

      © 2013 Royal College of Pathologists of Australasia. Published by Elsevier Inc. All rights reserved.

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