Abstract：
OBJECTIVE: IDH-wildtype (IDHwt) diffuse gliomas are treated as glioblastoma, however, some of these may show less aggressive clinical courses. The authors investigated the clinical, histopathological, and molecular characteristics of such IDHwt indolent diffuse gliomas (iDGwt), which have not been well documented in the literature.
METHODS: Adult patients with IDHwt gliomas admitted between 2011 and 2020 were surveyed. In this particular study, the clinical indolence was defined mainly as having a small enhancing lesion and a stable period for more than 1 month before surgery. The current WHO diagnostic criteria were adapted for the diagnoses. Gene mutations and copy number changes in 43 representative glioma-associated genes, MGMT promoter methylation status, and survival data were compared with those of The Cancer Genome Atlas reference cohort.
RESULTS: Nine out of 180 surveyed cases (5.0%) fulfilled the present criteria of the iDGwt. Considering the representative regulatory pathways, 8 (88.9%), 4 (44.4%), and 1 (11.1%) case had genetic alterations in the PI3K/MAPK, TP53, and RB pathways, respectively. The frequency of the RB pathway alteration was significantly lower than that in the reference cohort (281 of 362 cases: 77.6%). Two cases (22.2%) showing EGFR amplification met the diagnostic criteria for glioblastoma, and the frequency was significantly lower than that in the reference cohort (412 of 426 cases: 96.7%). The overall survival (median: 37.5 months) in the present series was significantly longer than that in the reference cohort (n = 426, median: 13.9 months).
CONCLUSIONS: iDGwt lacked the molecular features of glioblastoma except for the PI3K/MAPK pathway alteration.
METHODS: Adult patients with IDHwt gliomas admitted between 2011 and 2020 were surveyed. In this particular study, the clinical indolence was defined mainly as having a small enhancing lesion and a stable period for more than 1 month before surgery. The current WHO diagnostic criteria were adapted for the diagnoses. Gene mutations and copy number changes in 43 representative glioma-associated genes, MGMT promoter methylation status, and survival data were compared with those of The Cancer Genome Atlas reference cohort.
RESULTS: Nine out of 180 surveyed cases (5.0%) fulfilled the present criteria of the iDGwt. Considering the representative regulatory pathways, 8 (88.9%), 4 (44.4%), and 1 (11.1%) case had genetic alterations in the PI3K/MAPK, TP53, and RB pathways, respectively. The frequency of the RB pathway alteration was significantly lower than that in the reference cohort (281 of 362 cases: 77.6%). Two cases (22.2%) showing EGFR amplification met the diagnostic criteria for glioblastoma, and the frequency was significantly lower than that in the reference cohort (412 of 426 cases: 96.7%). The overall survival (median: 37.5 months) in the present series was significantly longer than that in the reference cohort (n = 426, median: 13.9 months).
CONCLUSIONS: iDGwt lacked the molecular features of glioblastoma except for the PI3K/MAPK pathway alteration.
摘要：
目的：IDH-野生型（IDHwt）弥漫性胶质瘤被视为胶质母细胞瘤，然而,其中一些可能显示不太积极的临床课程。作者调查了临床，组织病理学,和这种IDHwt惰性弥漫性神经胶质瘤（iDGwt）的分子特征，这在文献中没有得到很好的记载。
方法：对2011年至2020年收治的IDHwt胶质瘤成年患者进行调查。在这项特殊的研究中，临床惰性的定义主要是有一个小的增强病变和手术前1个月以上的稳定期。目前的WHO诊断标准适用于诊断。43个代表性神经胶质瘤相关基因的基因突变和拷贝数变化，MGMT启动子甲基化状态,和生存数据与癌症基因组图谱参考队列进行了比较。
结果：180例调查病例中有9例（5.0％）符合iDGwt的当前标准。考虑到代表性的监管途径，8（88.9%），4（44.4%），1例(11.1%)PI3K/MAPK基因改变,TP53和RB途径，分别。RB通路改变的频率显着低于参考队列（362例中的281例：77.6％）。2例（22.2%）显示EGFR扩增符合胶质母细胞瘤的诊断标准，并且频率显着低于参考队列（426例中的412例：96.7％）。本系列的总生存期（中位数：37.5个月）明显长于参考队列（n=426，中位数：13.9个月）。
结论：iDGwt缺乏胶质母细胞瘤的分子特征，除了PI3K/MAPK通路改变。
方法：对2011年至2020年收治的IDHwt胶质瘤成年患者进行调查。在这项特殊的研究中，临床惰性的定义主要是有一个小的增强病变和手术前1个月以上的稳定期。目前的WHO诊断标准适用于诊断。43个代表性神经胶质瘤相关基因的基因突变和拷贝数变化，MGMT启动子甲基化状态,和生存数据与癌症基因组图谱参考队列进行了比较。
结果：180例调查病例中有9例（5.0％）符合iDGwt的当前标准。考虑到代表性的监管途径，8（88.9%），4（44.4%），1例(11.1%)PI3K/MAPK基因改变,TP53和RB途径，分别。RB通路改变的频率显着低于参考队列（362例中的281例：77.6％）。2例（22.2%）显示EGFR扩增符合胶质母细胞瘤的诊断标准，并且频率显着低于参考队列（426例中的412例：96.7％）。本系列的总生存期（中位数：37.5个月）明显长于参考队列（n=426，中位数：13.9个月）。
结论：iDGwt缺乏胶质母细胞瘤的分子特征，除了PI3K/MAPK通路改变。
