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


Among more than 200 <i>BAP1</i>-mutant families affected by the "BAP1 cancer syndrome," nearly all individuals inheriting a <i>BAP1</i> 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 <i>BAP1</i> 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, <i>BAP1</i> has emerged as a key regulator of gene-environment interaction.<i>This article is highlighted in the In This Issue feature, p. 1079</i>.

  • Bononi A
  • Brugarolas J
  • Carbone M
  • Dey A
  • Gaudino G
  • Harbour JW
  • Krausz T
  • Pagano I
  • Pass HI
  • Yang H
PubMed ID
Appears In
Cancer Discov, 2020, 10 (8)