BAP1 in cancer: epigenetic stability and genome integrity

Our plain-English summary of BAP1 in cancer: epigenetic stability and genome integrity, by S. Caporali, A. Butera, I. Amelio (Discover Oncology, 2022).

The study

• Authors: S. Caporali, A. Butera, I. Amelio
• Journal: Discover Oncology
• Published: 2022;13(1):117
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mutations in BAP1 have been identified in a hereditary cancer predisposition syndrome and in sporadic tumours. Individuals carrying familiar BAP1 monoallelic mutations display hypersusceptibility to exposure-associated cancers, such as asbestos-driven mesothelioma, thus BAP1 status has been postulated to participate in gene-environment interaction. Intriguingly, BAP1 functions display also a high degree of tissue dependency, associated to a peculiar cancer spectrum and cell types of specific functions. Mechanistically, BAP1 functions as an ubiquitin carboxy-terminal hydrolase (UCH) and controls regulatory ubiquitination of histones as well as degradative ubiquitination of a range of protein substrates. In this article we provide an overview of the most relevant findings on BAP1, underpinning its tissue specific tumour suppressor function. We also discuss the importance of its epigenetic role versus the control of protein stability in the regulation of genomic integrity.

© 2022. The Author(s).

In plain English

This article is a perspective (a narrative review) in which the authors discussed published research on the BAP1 gene in cancer; it reported no new patients or experiments. The authors described the "BAP1 cancer syndrome": people carrying one inherited faulty copy of BAP1 show a high frequency of malignant mesothelioma, uveal melanoma and clear cell renal cell carcinoma, and more than 80% of gene carriers are affected by at least one type of cancer. They described BAP1 as a proposed example of gene-environment interaction, particularly for asbestos-associated mesothelioma. Summarising cell and mouse studies, they reported that losing BAP1 has effects that depend on cell type: deletion in mouse melanocytes and mesothelial cells led to proliferation. For mesothelioma, they noted that how BAP1 loss interacts with other frequent gene deletions (Cdkn2a/b and Nf2) has not been fully elucidated. The authors concluded that important questions remain, including why BAP1 loss is linked to this particular cancer spectrum and how much its epigenetic role matters compared with its other functions.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Perspective article (narrative review of published literature); no original data
• Who was studied: No study population; the authors reviewed published literature on BAP1, including studies in human cell lines, mouse models and BAP1 mutation carriers
• Exposure: Germline (inherited) and sporadic BAP1 mutations or inactivation, discussed as interacting with environmental exposures such as asbestos (for mesothelioma) and UV light (for melanoma). The article lists asbestos as six natural fibres: crocidolite, actinolite, tremolite, anthophyllite, amosite and chrysotile.
• Main results:
  • The authors report from the literature that people carrying a germline monoallelic BAP1 mutation show a high frequency of malignant mesothelioma, uveal melanoma and clear cell renal cell carcinoma
  • The authors state that more than 80% of BAP1 gene carriers are affected by at least one type of cancer, and that 90% of affected individuals have at least two close first-degree relatives with cancer
  • BAP1 mutation has been proposed as a key prototype of gene-environment interaction
  • From cell and mouse studies, the authors report that BAP1's tumour suppressor activity depends on cell type and context; BAP1 deletion in mouse primary melanocytes and mesothelial cells induced proliferation
  • In malignant mesothelioma, frequent deletions of the tumour suppressors Cdkn2a/b and Nf2 have been observed alongside BAP1 mutations; how these events interact with BAP1 inactivation has not been fully elucidated
• The authors' conclusion: The authors concluded that important questions remain unanswered: why BAP1 loss is linked to a selective cancer spectrum, and how relevant BAP1's epigenetic role is compared with its other described functions. They added that understanding of the underlying mechanisms has not yet led to therapeutic strategies.

Topics

Medical terms in this study, explained in our Lexicon: BAP1, Mesothelioma.

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