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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 01, 2020
- Source ID
- 10.1158/2159-8290.cd-19-1220
Entities
People
- Angela Bononi
- Anwesha Dey
- Giovanni Gaudino
- Haining Yang
- Harvey I Pass
- Ian Pagano
- J William Harbour
- James Brugarolas
- Michele Carbone
- Thomas Krausz
Organizations
- Genentech
- National Cancer Institute
- National Institute of Environmental Health Sciences
- National Institutes of Health
- New York University
- United States Department of Defense
- University of Chicago
- University of Miami