Pastorino S, et al. - Researchers investigated if malignant mesotheliomas (MMs) probably connected to germline mutations of BAP1 or of other genes could be identified with the help of four criteria: family history of MM, BAP1-associated cancers, multiple malignancies, or age younger than 50 years. A subset of patients with MM who had significantly improved survival was more easily recognized via these criteria. Many of these patients were unaware of asbestos exposure and additionally had either pathogenic germline mutations of BAP1 or additional genes linked to cancer, and some of these may have options for targeted-therapy. In view of the increased susceptibility to additional cancers, genetic counseling and cancer screening should be considered for these patients and their relatives.

Methods

• Researchers identified 79 patients with MM over the course of 7 years who met the four criteria.
• Possible asbestos exposure was reported in 22 of the 79 (28%).
• They screened the patients for germline BAP1 mutations by Sanger sequencing and by targeted next-generation sequencing (tNGS) for germline mutations in 55 additional cancer-linked genes.
• Validation of deleterious mutations detected by tNGS was performed using Sanger sequencing.

Results

• Deleterious germline BAP1 mutations were identified in 43/79 patients (16 probands and 27 relatives).
• The patients had the median age of 54 years at diagnosis and displayed median survival of 5 years.
• A median age of 45 years at diagnosis was determined among the remaining 36 patients without BAP1 mutation, and they displayed a median survival of 9 years; 12 had harmful mutations of additional genes linked to cancer.
• When compared with patients with MMs in the SEER cohort, significantly different median age at diagnosis (72 years), median survival for all MM stages (8 months), and stage I (11 months) from the 79 patients with MM in the current study were evident (P < .0001).