Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer.

IF 2.1 4区 医学 Q3 GENETICS & HEREDITY
Fangfang Gao, Dejian Gu, He Zhang, Chao Shi, Feng Du, Bo Zheng, Huijuan Wu, Yanqiu Zhao
{"title":"Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer.","authors":"Fangfang Gao, Dejian Gu, He Zhang, Chao Shi, Feng Du, Bo Zheng, Huijuan Wu, Yanqiu Zhao","doi":"10.1186/s12920-024-01957-w","DOIUrl":null,"url":null,"abstract":"<p><p>Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331603/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Medical Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12920-024-01957-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.

病例报告:对免疫疗法的反应以及遗传性骨髓瘤病和肾细胞癌相关肾细胞癌中 fh 基因的关联。
遗传性肌壁间白血病和肾细胞癌(HLRCC)是一种罕见的常染色体显性遗传综合征,由富马酸氢化酶(FH)基因的种系突变引起,表现为皮肤肌壁间白血病、子宫肌瘤和肾细胞癌(RCC)。HLRCC相关RCC(HLRCC-RCC)患者的临床病程具有侵袭性,但目前还没有针对晚期HLRCC-RCC的标准化疗法。在本研究中,我们描述了一例侵袭性 HLRCC 病例,患者是一名 33 岁女性,她的 FH 基因第 8 外显子中存在一个新型杂合子种系插入突变(c.1126 C > T; p.Q376*)。患者接受了腹腔镜右肾切除术,但术后 3 个月内出现转移。切除肿瘤的组织学染色显示,程序性细胞死亡配体1(PD-L1)的表达水平很高。因此,患者接受了免疫治疗。患者对免疫疗法取得了部分应答,转移病灶的治疗效果也不断改善。通过全面的文献回顾,我们找到了 76 例接受过免疫疗法的 HLRCC-RCC 病例。本研究从中选择了 46 例患者,仔细研究 FH 基因突变与免疫治疗效果之间的关系。我们的研究结果表明,免疫疗法可明显改善HLRCC-RCC患者的总生存期(OS)。然而,我们没有观察到FH种系基因不同突变对免疫疗法疗效的影响。因此,我们的研究表明,无论FH基因突变类型如何,免疫疗法对HLRCC患者都是一种有效的治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
BMC Medical Genomics
BMC Medical Genomics 医学-遗传学
CiteScore
3.90
自引率
0.00%
发文量
243
审稿时长
3.5 months
期刊介绍: BMC Medical Genomics is an open access journal publishing original peer-reviewed research articles in all aspects of functional genomics, genome structure, genome-scale population genetics, epigenomics, proteomics, systems analysis, and pharmacogenomics in relation to human health and disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信