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Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer.

ABSTRACT: Among more than 200 BAP1-mutant families affected by the "BAP1 cancer syndrome," nearly all individuals inheriting a BAP1 mutant allele developed one or more malignancies during their lifetime, mostly uveal and cutaneous melanoma, mesothelioma, and clear-cell renal cell carcinoma. These cancer types are also those that, when they occur sporadically, are more likely to carry somatic biallelic BAP1 mutations. Mechanistic studies revealed that the tumor suppressor function of BAP1 is linked to its dual activity in the nucleus, where it is implicated in a variety of processes including DNA repair and transcription, and in the cytoplasm, where it regulates cell death and mitochondrial metabolism. BAP1 activity in tumor suppression is cell type- and context-dependent. BAP1 has emerged as a critical tumor suppressor across multiple cancer types, predisposing to tumor development when mutated in the germline as well as somatically. Moreover, BAP1 has emerged as a key regulator of gene-environment interaction.This article is highlighted in the In This Issue feature, p. 1079.

SUBMITTER: Carbone M

PROVIDER: S-EPMC8006752 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer.

Carbone Michele M Harbour J William JW Brugarolas James J Bononi Angela A Pagano Ian I Dey Anwesha A Krausz Thomas T Pass Harvey I HI Yang Haining H Gaudino Giovanni G

Cancer discovery 20200720 8

Among more than 200 BAP1-mutant families affected by the "BAP1 cancer syndrome," nearly all individuals inheriting a BAP1 mutant allele developed one or more malignancies during their lifetime, mostly uveal and cutaneous melanoma, mesothelioma, and clear-cell renal cell carcinoma. These cancer types are also those that, when they occur sporadically, are more likely to carry somatic biallelic BAP1 mutations. Mechanistic studies revealed that the tumor suppressor function of B ...[more]

PMID: 32690542

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Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer.

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Biological Mechanisms and Clinical Significance of <i>BAP1</i> Mutations in Human Cancer.

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