Mesothelioma: Identification of the Key Molecular Events Triggered by BAP1
Technical Report,15 Aug 2013,14 Aug 2014
University of Hawaii Cancer Center Honolulu United States
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We discovered that germline BAP1 mutations cause a novel cancer syndrome characterized by a very high incidence of MM. In some BAP1-mutation carrying families, MM accounts for more than 50 of deaths. We hypothesize that this may be due to increased susceptibility to MM from exposure to modest amounts of asbestos that would normally not cause MM in the population at large. In order to study the mechanisms, we assembled a unique cohort and set of reagents. We have conducted a number of in vitro and in vivo experiments and obtained quite exciting results during this year. We found that BAP1 status regulate NF-kB activity and HMGB1 release, and we also found that monoallelic BAP1 loss increases susceptibility to low doses of asbestos by using a mouse model.