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C. Villenet
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-015 - BAP1 is Inactivated by Copy Number Loss, Mutation, and/or Loss of Expression in More Than 70% Malignant Peritoneal Mesotheliomas (ID 4575)
14:30 - 14:30 | Author(s): C. Villenet
- Abstract
Background:
Breast cancer type 1 susceptibility associated protein (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes and acts as a tumor suppressor gene. Malignant mesothelioma is a deadly disease strongly associated with asbestos exposure. Most of the cases (70%) are pleural mesotheliomas while peritoneal and pericardial mesotheliomas account for 25% and 5%, respectively. Germ-line and somatic inactivation of BAP1 has been recurrently reported in pleural mesothelioma. However, due to its rarity and challenging diagnosis, little is known about the BAP1 status in peritoneal mesothelioma, with the largest series so far sequenced including only 12 tumors.
Methods:
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. In order to determine the status of BAP1 in these samples, three different levels were evaluated: copy number changes by comparative genomic hybridization arrays (Chirac et al., Human Path 2016), mutations by next-generation sequencing, and protein expression by immunohistochemistry.
Results:
We detected copy number losses, mutations, and/or loss of expression of BAP1 in 42.2%, 33.3%, and 56.8% of the malignant peritoneal mesotheliomas analyzed, respectively. In most of the cases with additional data available (13/16), the loss of BAP1 expression was explained by co-occurring copy number loss and/or mutation. Overall, 73.2% of the malignant peritoneal mesotheliomas analyzed carried an inactivated BAP1 gene. In addition, BAP1 mutations were exclusively detected in males and a better overall survival was observed for patients with loss of BAP1 expression independently of age, sex, smoking and asbestos exposures (p=0.03).
Conclusion:
Inactivation of BAP1 seems to have a key role in the development of both pleural and peritoneal mesotheliomas. In addition, we found that loss of BAP1 expression in peritoneal mesotheliomas was mostly explained by copy number losses and mutations, and was associated with a better overall survival.
