10111-MPC-11 CLINICAL AND MOLECULAR NEUROPATHOLOGICAL FEATURES OF EPITHELIOID GLIOBLASTOMA

Takeo Uzuka, Takuma Sumi, Hadzuki Matsuda, Hiroyoshi Akutsu
{"title":"10111-MPC-11 CLINICAL AND MOLECULAR NEUROPATHOLOGICAL FEATURES OF EPITHELIOID GLIOBLASTOMA","authors":"Takeo Uzuka, Takuma Sumi, Hadzuki Matsuda, Hiroyoshi Akutsu","doi":"10.1093/noajnl/vdad141.049","DOIUrl":null,"url":null,"abstract":"Abstract BACKGROUND Epithelioid Glioblastoma (E-GBM) has been identified as a pathological subtype of Glioblastoma. It is a rare glioblastoma and is mainly known in case reports, and the details of its clinical features and genetic characteristics are not clear. Here, we retrospecivly studied the results of clinical course and genetic features of E-GBM. METHODS Four patients who underwent surgery at our institution and were diagnosed with E-GBM were included in this study. Histological diagnosis was obtained by surgical excision in all cases. We extracted DNA from the resected tissues and analyzed glioma-related genes using various methods such as high resolution melting (HRM), MGMT methylation-specific HRM, digital PCR, and Multiple ligation-dependent probe amplification (MLPA) analysis. Moreover, we assayed methylation EPIC BeadChip arrays for each sample. RESULTS E-GBM tended to develop at a slightly younger age than other general glioblastoma. All patients underwent surgical resection followed by radiation therapy and concurrent temozolomide therapy. However, none of the patients were able to transition to temozolomide maintenance therapy due to disease progression, and the overall survival period was 8 to 19 weeks, indicating an extremely poor prognosis. Genetic analysis revealed both TERT promoter mutations and BRAFV600E mutation in all cases. In addition, IDH mutation was not found, and MGMT promoter methylation was unmethylated in all cases. EGFR amplification, CDKN2A/2B homozygous deletion and 1p/19q co-deletion were not found in any cases. Methylation-based classification did not reach E-GBM in all samples. CONCLUSION The simultaneous mutations of TERT promoter with BRAFV600E could serve as diagnostic molecular markers for the diagnosis of E-GBM. Standard therapy for glioblastoma was not expected to be effective in treating this tumor. It was considered necessary to introduce new therapeutic strategies such as early administration of BRAF and MEK inhibitors.","PeriodicalId":19138,"journal":{"name":"Neuro-oncology Advances","volume":" 7","pages":"v12 - v13"},"PeriodicalIF":0.0000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuro-oncology Advances","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/noajnl/vdad141.049","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Abstract BACKGROUND Epithelioid Glioblastoma (E-GBM) has been identified as a pathological subtype of Glioblastoma. It is a rare glioblastoma and is mainly known in case reports, and the details of its clinical features and genetic characteristics are not clear. Here, we retrospecivly studied the results of clinical course and genetic features of E-GBM. METHODS Four patients who underwent surgery at our institution and were diagnosed with E-GBM were included in this study. Histological diagnosis was obtained by surgical excision in all cases. We extracted DNA from the resected tissues and analyzed glioma-related genes using various methods such as high resolution melting (HRM), MGMT methylation-specific HRM, digital PCR, and Multiple ligation-dependent probe amplification (MLPA) analysis. Moreover, we assayed methylation EPIC BeadChip arrays for each sample. RESULTS E-GBM tended to develop at a slightly younger age than other general glioblastoma. All patients underwent surgical resection followed by radiation therapy and concurrent temozolomide therapy. However, none of the patients were able to transition to temozolomide maintenance therapy due to disease progression, and the overall survival period was 8 to 19 weeks, indicating an extremely poor prognosis. Genetic analysis revealed both TERT promoter mutations and BRAFV600E mutation in all cases. In addition, IDH mutation was not found, and MGMT promoter methylation was unmethylated in all cases. EGFR amplification, CDKN2A/2B homozygous deletion and 1p/19q co-deletion were not found in any cases. Methylation-based classification did not reach E-GBM in all samples. CONCLUSION The simultaneous mutations of TERT promoter with BRAFV600E could serve as diagnostic molecular markers for the diagnosis of E-GBM. Standard therapy for glioblastoma was not expected to be effective in treating this tumor. It was considered necessary to introduce new therapeutic strategies such as early administration of BRAF and MEK inhibitors.
10111-MPC-11 上皮样胶质母细胞瘤的临床和分子神经病理学特征
上皮样胶质母细胞瘤(E-GBM)已被确定为胶质母细胞瘤的病理亚型。它是一种罕见的胶质母细胞瘤,主要见于病例报道,其临床特征和遗传特征的细节尚不清楚。在这里,我们回顾性研究了E-GBM的临床病程和遗传特征的结果。方法4例在我院接受手术诊断为E-GBM的患者纳入本研究。所有病例均通过手术切除获得组织学诊断。我们从切除的组织中提取DNA,并使用各种方法分析胶质瘤相关基因,如高分辨率融化(HRM)、MGMT甲基化特异性HRM、数字PCR和多重连接依赖探针扩增(MLPA)分析。此外,我们分析了每个样品的甲基化EPIC BeadChip阵列。结果E-GBM的发病年龄比其他一般胶质母细胞瘤稍早。所有患者均行手术切除,放疗和替莫唑胺联合治疗。然而,由于疾病进展,没有患者能够过渡到替莫唑胺维持治疗,总生存期为8 ~ 19周,预后极差。遗传分析显示所有病例均存在TERT启动子突变和BRAFV600E突变。此外,未发现IDH突变,所有病例的MGMT启动子甲基化均未甲基化。未发现EGFR扩增、CDKN2A/2B纯合缺失和1p/19q共缺失。在所有样本中,基于甲基化的分类未达到E-GBM。结论TERT启动子与BRAFV600E同时突变可作为诊断E-GBM的诊断分子标记。胶质母细胞瘤的标准治疗被认为不能有效治疗这种肿瘤。人们认为有必要引入新的治疗策略,如早期给予BRAF和MEK抑制剂。
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
自引率
0.00%
发文量
0
×
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