Biological mechanisms and clinical signifi cance of BAP1 mutations in human cancer

Michele Carbone, J. William Harbour, James Brugarolas, Angela Bononi, Ian Pagano, Anwesha Dey, Thomas Krausz, Harvey I. Pass, Haining Yang, Giovanni Gaudino

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1103-1120
Number of pages18
JournalCancer discovery
Issue number8
StatePublished - 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology


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