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.
Flavia Novelli, Angela Bononi, Qian Wang, Fang Bai, Simone Patergnani, Franz Kricek, Ellinor Haglund, Joelle S. Suarez, Mika Tanji, Ronghui Xu, Yasutaka Takanishi, Michael Minaai, Sandra Pastorino, Paul Morris, Greg Sakamoto, Harvey I. Pass, Haithem Barbour, Giovanni Gaudino, Carlotta Giorgi, Paolo Pinton, Jose N. Onuchic, Haining Yang, and Michele Carbone.