BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos

This is the authors' abstract. We don't add key points for this paper.

Significance Our findings explain mechanistically the observed gene × environment (G×E) interaction in mesotheliomas occurring in carriers of heterozygous germline BAP1 mutations ( BAP1 +/− ) exposed to asbestos. The increased amount of acetylated HMGB1 can be measured in the serum and may prove useful as a diagnostic/prognostic biomarker of mesothelioma in BAP1 +/− individuals. Inhibition of HMGB1 secretion in Bap1 +/− mutant mice exposed to asbestos significantly decreased the incidence of mesothelioma and prolonged the survival of those who developed mesothelioma. This strategy may be translated to carriers of germline BAP1 mutations with the aim of decreasing their incidence of mesothelioma.