Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children: A Retrospective Series of 164 Cases.
Diffuse Midline Gliomas With Histone H3 K27M Mutation in Adults and Children: A Retrospective Series of 164 Cases.
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成人和儿童中组蛋白 H3 K27M 突变的弥漫性中线胶质瘤
DOI：
10.1097/pas.0000000000001897
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发表时间：
2022-06-01
影响因子：
5.6
通讯作者：
Chen, Ni
中科院分区：
文献类型：
--
作者：
Zheng, Linmao;Gong, Jing;Yu, Tianping;Zou, Yan;Zhang, Mengni;Nie, Ling;Chen, Xueqin;Yue, Qiang;Liu, Yanhui;Mao, Qing;Zhou, Qiao;Chen, Ni
弥漫性中线胶质瘤 H3 K27M 突变型 (H3 K27M-mt DMG) 是一种罕见且高度侵袭性的肿瘤，在儿童中比成人更常见。很少有研究比较患有这种罕见肿瘤的儿童和成人患者之间的差异。我们在此报告对 94 例成人和 70 例儿童弥漫性中线胶质瘤病例的回顾性研究。通过常规组织病理学和免疫组织化学分析手术肿瘤样本中的 H3 K27M、IDH1 R132H、ATRX、p53、OLIG2、胶质纤维酸性蛋白和 Ki-67； H3F3A、HIST1H3B、IDH1、IDH2、TERT、BRAF等基因热点突变点Sanger测序；以及O 6 -甲基鸟嘌呤DNA甲基转移酶启动子甲基化的甲基化特异性聚合酶链式反应。成人和儿童患者最常见的解剖位置分别是丘脑和脑干。分子分析显示，成人中 ATRX 丢失和 H3.3 突变的频率高于儿童 H3 K27M-mt DMG。在儿童患者中未检测到 TERT 启动子突变和 O 6 -甲基鸟嘌呤 DNA 甲基转移酶启动子甲基化，但在少数成人患者中存在。随访期间，93/122例患者（70.1%）死于该病，中位生存时间为10.5个月（范围：1至104个月）。 Kaplan-Meier 分析表明，成人患者的预后优于儿科患者 (P=0.0003)。多变量分析表明患者年龄、原发肿瘤大小、ATRX 表达状态和 Ki-67 指数是独立的预后因素。本研究表明，成人和儿童 H3 K27M-mt DMG 在肿瘤的解剖位置、分子变化和预后方面存在差异。
Diffuse midline glioma, H3 K27M-mutant (H3 K27M-mt DMG), is a rare and highly aggressive tumor that is more common in children than in adults. Few studies have compared the differences between pediatric and adult patients with this rare tumor. We here report our retrospective study of 94 adult and 70 pediatric cases of diffuse midline glioma. Surgical tumor samples were analyzed by routine histopathology and immunohistochemistry for H3 K27M, IDH1 R132H, ATRX, p53, OLIG2, glial fibrillary acidic protein, and Ki-67; Sanger sequencing for hot mutation spots in genes including H3F3A, HIST1H3B, IDH1, IDH2, TERT, and BRAF; and methylation-specific polymerase chain reaction for O 6 -methylguanine DNA methyltransferase promoter methylation. The most frequent anatomic locations in adult and pediatric patients were the thalamus and brainstem, respectively. Molecular profiling revealed higher frequencies of ATRX loss and H3.3 mutation in adult than in pediatric H3 K27M-mt DMGs. TERT promoter mutations and O 6 -methylguanine DNA methyltransferase promoter methylation were not detected in pediatric patients but were present in a few adult patients. During the follow-up period, 93/122 patients (70.1%) died from the disease, with a median survival time of 10.5 months (range: 1 to 104 mo). Kaplan-Meier analyses demonstrated that the prognosis was better for adult patients than the pediatric cohort (P=0.0003). Multivariate analyses indicated that patient age, primary tumor size, status of ATRX expression, and Ki-67 index were independent prognosticators. The present study showed that there were differences between adult and pediatric H3 K27M-mt DMGs in terms of the anatomic location of tumor, molecular changes, and prognosis.