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Germline variants predispose to mesothelioma by impairing DNA repair and calcium signaling.胚系变异通过损害 DNA 修复和钙信号传导而导致间皮瘤易感性。
Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2405231121. doi: 10.1073/pnas.2405231121. Epub 2024 Jul 11.
2
Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial.帕博利珠单抗联合化疗对比单纯化疗用于未经治疗的加拿大、意大利和法国晚期胸膜间皮瘤的 3 期、开放标签、随机对照临床试验。
Lancet. 2023 Dec 16;402(10419):2295-2306. doi: 10.1016/S0140-6736(23)01613-6. Epub 2023 Nov 3.
3
BAP1 Loss by Immunohistochemistry Predicts Improved Survival to First-Line Platinum and Pemetrexed Chemotherapy for Patients With Pleural Mesothelioma: A Validation Study.免疫组织化学检测 BAP1 缺失可预测恶性胸膜间皮瘤患者一线铂类和培美曲塞化疗的生存获益:一项验证性研究。
J Thorac Oncol. 2022 Jul;17(7):921-930. doi: 10.1016/j.jtho.2022.04.008. Epub 2022 Apr 27.
4
Medical and Surgical Care of Patients With Mesothelioma and Their Relatives Carrying Germline BAP1 Mutations.间皮瘤患者及其携带胚系 BAP1 突变的亲属的医疗和手术护理。
J Thorac Oncol. 2022 Jul;17(7):873-889. doi: 10.1016/j.jtho.2022.03.014. Epub 2022 Apr 21.
5
Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma.中国肾细胞癌患者的胚系突变图谱及相关临床特征
Front Oncol. 2021 Dec 2;11:737547. doi: 10.3389/fonc.2021.737547. eCollection 2021.
6
The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families.中国家族性/遗传性乳腺癌家庭中多种癌症易感性基因的突变景观。
Cancer Biol Med. 2021 Sep 28;19(6):850-70. doi: 10.20892/j.issn.2095-3941.2021.0011.
7
Alterations in Are Associated with Cisplatin Resistance through Inhibition of Apoptosis in Malignant Pleural Mesothelioma.这些改变与顺铂耐药性有关,通过抑制恶性胸膜间皮瘤细胞凋亡。
Clin Cancer Res. 2021 Apr 15;27(8):2277-2291. doi: 10.1158/1078-0432.CCR-20-4037. Epub 2021 Feb 5.
8
First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial.一线纳武利尤单抗联合伊匹单抗治疗不可切除恶性胸膜间皮瘤(CheckMate 743):一项多中心、随机、开放标签、III 期临床试验。
Lancet. 2021 Jan 30;397(10272):375-386. doi: 10.1016/S0140-6736(20)32714-8. Epub 2021 Jan 21.
9
Biological Mechanisms and Clinical Significance of Mutations in Human Cancer.人类癌症突变的生物学机制和临床意义。
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10
BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma.BAP1 杂合性缺失预测恶性腹膜间皮瘤具有独特的免疫原性。
Genome Med. 2019 Feb 18;11(1):8. doi: 10.1186/s13073-019-0620-3.

采用双重免疫检查点抑制剂治疗的伴有新型种系移码突变的恶性间皮瘤:病例报告

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

作者信息

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

机构信息

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.

出版信息

Oncol Lett. 2025 May 21;30(1):358. doi: 10.3892/ol.2025.15104. eCollection 2025 Jul.

DOI:10.3892/ol.2025.15104
PMID:40463358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12130912/
Abstract

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.

摘要

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。