TY - JOUR
T1 - Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer
AU - Carbone, Michele
AU - Harbour, J. William
AU - Brugarolas, James
AU - Bononi, Angela
AU - Pagano, Ian
AU - Dey, Anwesha
AU - Krausz, Thomas
AU - Pass, Harvey I.
AU - Yang, Haining
AU - Gaudino, Giovanni
N1 - Publisher Copyright:
©2020 American Association for Cancer Research.
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
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U2 - 10.1158/2159-8290.CD-19-1220
DO - 10.1158/2159-8290.CD-19-1220
M3 - Review article
C2 - 32690542
AN - SCOPUS:85089127992
VL - 10
SP - 1103
EP - 1120
JO - Cancer Discovery
JF - Cancer Discovery
SN - 2159-8274
IS - 8
ER -