BAP1 is altered by copy number loss, mutation, and/or loss of protein expression in more than 70% malignant peritoneal mesotheliomas

Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer 2016 December 27 [Epub ahead of print] [Link]

Leblay N, Leprêtre F, Le Stang N, Gautier-Stein A, Villeneuve L, Isaac S, Maillet D, Galateau-Sallé F, Villenet C, Sebda S, Goracci A, Byrnes G, McKay JD, Figeac M, Glehen O, Gilly FN, Foll M, Fernandez-Cuesta L, Brevet M


Malignant mesothelioma is a deadly disease strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BAP1 is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germ-line and somatic inactivation of BAP1 is frequent in pleural mesothelioma, however, little is known about its status in peritoneal mesothelioma.
Taking advantage of the extensive French national networks MESOPATH and RENAPE, we collected biological material and clinical and epidemiological data for 46 peritoneal mesothelioma patients. The status of BAP1 was evaluated at the mutational and protein expression levels and combined with our previous data on copy number alterations assessed in the same samples.
We detected mutations in 32% of the malignant peritoneal mesotheliomas analyzed. In addition, we have previously reported that copy number losses occurred in 42% of the samples included in this series. Overall, 71% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but only 57% have a complete loss of its protein nuclear expression. A better overall survival was observed for patients with BAP1 mutations (p=0.04), protein expression loss (p=0.016), or at least one of these alterations (p=0.007) independently of tumor histology, age, and gender.
Similar to pleural mesothelioma, inactivation of BAP1 is frequent in peritoneal mesotheliomas. We found that BAP1 protein nuclear expression is a good prognostic factor and a more reliable marker for the complete loss of BAP1 activity, than mutation or copy number loss.