Malignant mesothelioma with a novel BAP1 germline frameshift mutation treated with dual immune checkpoint inhibitors: A case report

Oncology Letters 2025 May 21 [Link]

Na Zhou, Mingying Wu, Chenyu Wang, Mingming Yuan, Yuejuan Cheng Huanwen Wu, Xin Gao, Shuangni Yu, Lin Zhao

Abstract

Germline pathogenic mutation of the BAP1 gene is a common molecular event in malignant mesothelioma (MM). A patient with a positive family history of tenacious peritoneal effusions presented with hydropneumothorax and suffered from recurrent pleural and peritoneal effusions since. Tuberculosis (TB) was assumed by preceding clinicians who prescribed futile anti-TB regimens. Finally, a diagnostic laparoscopy and omental biopsy revealed the histology of MM. Next-generation sequencing uncovered a novel BAP1 germline frameshift mutation (c. 1077_1083delinsTG, pPhe360fs), which was rated as pathogenic due to its potential to introduce a termination codon, resulting in nonsense-mediated mRNA decay and due to the fact of BAP1 protein nuclear loss in tumor tissue. Dual immunotherapy with nivolumab and ipilimumab was given for 3 cycles and only achieved stable disease. Steven-Johnson syndrome occurred afterward and was relieved after steroid treatment. The present study reported a case of MM with a new BAP1 frameshift mutation, treated by dual immune checkpoint inhibitors, achieving a modest drug effect and serious skin-related adverse events.