Zhou Na, Wu Mingying, Wang Chenyu, Yuan Mingming, Cheng Yuejuan, Wu Huanwen, Gao Xin, Yu Shuangni, Zhao Lin
Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, P.R. China.
Geneplus-Beijing, Beijing 102206, P.R. China.
Oncol Lett. 2025 May 21;30(1):358. doi: 10.3892/ol.2025.15104. eCollection 2025 Jul.
Germline pathogenic mutation of the 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 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 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 frameshift mutation, treated by dual immune checkpoint inhibitors, achieving a modest drug effect and serious skin-related adverse events.
该基因的种系致病突变是恶性间皮瘤(MM)中常见的分子事件。一名有顽固性腹腔积液家族史的患者出现气胸,此后反复出现胸腔和腹腔积液。之前的临床医生怀疑是结核病,并使用了无效的抗结核方案。最后,诊断性腹腔镜检查和网膜活检显示为MM组织学。二代测序发现了一种新的种系移码突变(c.1077_1083delinsTG,pPhe360fs),由于其可能引入终止密码子,导致无义介导的mRNA降解,以及肿瘤组织中蛋白质核丢失,被评为致病性突变。给予纳武单抗和伊匹单抗联合免疫治疗3个周期,仅达到疾病稳定。随后发生了史蒂文斯-约翰逊综合征,经类固醇治疗后缓解。本研究报告了一例具有新的移码突变的MM病例,采用双重免疫检查点抑制剂治疗,取得了适度的药物疗效和严重的皮肤相关不良事件。