Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy

Authors: Raffit Hassan, Betsy Morrow, Anish Thomas, Tom Walsh, Ming K. Lee, Süleyman Gülsüner, Meghana Gadiraju, Vasiliki Panou, Shaojian Gao, Idrees Mian, Javed Khan, Mark Raffeld, Snehal Patel, Liqiang Xi, Jun S. Wei, Mary Hesdorffer, Jingli Zhang, Kathleen Calzone, Arpita Desai, Emerson Padiernos, Christine Alewine, David S. Schrump, Seth M. Steinberg, Hedy L. Kindler, Mary‐Claire King, Jane Churpek - Proceedings of the National Academy of Sciences, PNAS 2019 cited by 156

Significance Survival from malignant mesothelioma, particularly pleural mesothelioma, is very poor. For patients with some cancers, overall survival following platinum chemotherapy is better for patients with germline mutations in DNA repair and related genes than for patients without such mutations. We evaluated this relationship for patients with malignant mesothelioma. Following platinum chemotherapy, overall survival was significantly longer for patients with loss-of-function mutations in BAP1 and DNA repair genes compared with patients with no such mutations. The effect of genotype was highly significant for patients with pleural mesothelioma, but not for patients with peritoneal mesothelioma, and remained significant after adjusting for gender and age at diagnosis. These patients may benefit from DNA repair targeted therapies such as poly-ADP ribose polymerase inhibitors.