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J Thorac Oncol. 2017 Apr;12(4):724-733. doi: 10.1016/j.jtho.2016.12.019. Epub 2016 Dec 27.

BAP1 Is Altered by Copy Number Loss, Mutation, and/or Loss of Protein Expression in More Than 70% of Malignant Peritoneal Mesotheliomas.

Author information

1
International Agency for Research on Cancer, Lyon, France.
2
Structural and Functional Genomics Core Facility, University of Lille, Lille, France.
3
Department of Biopathology, Cancer Center Lyon Leon Berard, Lyon, France; National Cancer Institute, Research Unit 1086, Caen, France.
4
National Cancer Institute, Research Unit 1213, Lyon, France.
5
Faculty of Medicine, Research Team 3738, Lyon1 University, Oullins, France; French National Network for the Treatment of Rare Peritoneal Surface Malignancies, University Hospital of Lyon and Lyon1 University, Lyon, France; University Hospital of Lyon, Lyon, France.
6
Faculty of Medicine, Research Team 3738, Lyon1 University, Oullins, France; French National Network for the Treatment of Rare Peritoneal Surface Malignancies, University Hospital of Lyon and Lyon1 University, Lyon, France; Department of Pathology, University Hospital of Lyon and Lyon1 University, Lyon, France.
7
Department of Oncology, University Hospital of Lyon and Lyon1 University, Lyon, France.
8
Department of Radiology, University Hospital of Lyon and Lyon1 University, Lyon, France.
9
Structural and Functional Genomics Core Facility, University of Lille, Lille, France; Sequencing Platform, Research Cancer Institute, Lille, France.
10
Faculty of Medicine, Research Team 3738, Lyon1 University, Oullins, France; French National Network for the Treatment of Rare Peritoneal Surface Malignancies, University Hospital of Lyon and Lyon1 University, Lyon, France; Department of Surgery, University Hospital of Lyon and Lyon1 University, Lyon, France.
11
International Agency for Research on Cancer, Lyon, France. Electronic address: fernandezcuestal@iarc.fr.

Abstract

INTRODUCTION:

Malignant mesothelioma is a deadly disease that is strongly associated with asbestos exposure. Peritoneal mesotheliomas account for 10% of all the cases. BRCA1 associated protein 1 (BAP1) is a deubiquitinating hydrolase that plays a key role in various cellular processes. Germline and somatic inactivation of BRCA1 associated protein 1 gene (BAP1) is frequent in pleural mesothelioma; however, little is known about its status in peritoneal mesothelioma.

METHODS:

Taking advantage of the extensive French National Network for the Diagnosis of Malignant Pleural Mesothelioma and Rare Peritoneal Tumors and the French National Network for the Treatment of Rare Peritoneal Surface Malignancies, we collected biological material and clinical and epidemiological data for 46 patients with peritoneal mesothelioma. 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.

RESULTS:

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, 73% of the malignant peritoneal mesotheliomas analyzed carried at least one inactivated BAP1 allele, but only 57% had a complete loss of its protein nuclear expression. 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 histological subtype, age, and sex.

CONCLUSIONS:

As in 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.

KEYWORDS:

Malignant, BAP1; Mesothelioma; Peritoneal

PMID:
28034829
DOI:
10.1016/j.jtho.2016.12.019
[Indexed for MEDLINE]
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