@article{2b7bcaaeb100427eb07192c532701eae,
title = "Biological mechanisms and clinical signifi cance 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.",
author = "Michele Carbone and Harbour, {J. William} and James Brugarolas and Angela Bononi and Ian Pagano and Anwesha Dey and Thomas Krausz and Pass, {Harvey I.} and Haining Yang and Giovanni Gaudino",
note = "Funding Information: We thank all the family members affected by the BAP1 cancer syndrome and the patients with BAP1-mutated tumors who donated their specimens. They allowed us to study and discover how this gene functions in different cancer types and to translate this knowledge to improve cancer prevention, diagnosis, and prognosis (already being implemented), and in the near future, we hope, to improve therapies for patients with BAP1-mutated cancers. M. Carbone and H. Yang report funding from the National Institute of Environmental Health Sciences (NIEHS) 1R01ES030948-01 (to M. Carbone and H. Yang), the NCI 1R01CA237235-01A1 (to M. Carbone and H. Yang) and 1R01CA198138 (to M. Carbone), the U.S. Department of Defense (DoD) CA150671 (to H. Yang, M. Carbone, and H.I. Pass), and from the UH Foundation through donations from the Riviera United-4-a Cure (to M. Carbone and H. Yang), the Melohn Family Endowment, the Honeywell International Inc., the Germaine Hope Brennan Foundation, and the Maurice and Joanna Sullivan Family Foundation (to M. Carbone). M. Carbone is a board-certified pathologist who provides consultation for pleural pathology, including medical-legal. H.I. Pass and H. Yang report funding from the Early Detection Research Network NCI U01CA111295-08. H.I. Pass reports funding from Genentech, and Belluck and Fox LLP. J.W. Harbour reports funding from the Department of Defense W81XWH-15-1-0578, NIH R01 CA125970, P30CA240139 (to Sylvester Comprehensive Cancer Center), and P30EY014801 (to Bascom Palmer Eye Institute), Research to Prevent Blindness Unrestricted Grant (to Bascom Palmer Eye Institute), and a generous gift from Dr. Mark J. Daily. J. Brugarolas reports funding from the NIH 1P50CA196516, R01CA175754, and RP180192. Received November 14, 2019; revised February 3, 2020; accepted May 7, 2020; published first July 20, 2020. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
doi = "10.1158/2159-8290.CD-19-1220",
language = "English (US)",
volume = "10",
pages = "1103--1120",
journal = "Cancer discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "8",
}