Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 201 North Broadway, Viragh Building, 9th floor, Post Box 3, Baltimore, MD, 21287, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Neurooncol. 2019 May;143(1):87-93. doi: 10.1007/s11060-019-03134-x. Epub 2019 Mar 12.
H3 K27 mutations, most commonly in H3F3A, are common in diffuse midline glioma. The exact frequency of these mutations in adults with gliomas in the midline location is unknown. This study was conducted to define the incidence of H3 K27M mutations in this location and to compare clinicopathological features with those of patients who do not harbor this mutation.
Consecutive glioma cases from 2007 to 2017 were screened for gliomas in the midline location. Immunohistochemistry was performed on all available tissue for mutations of H3 K27M, IDH1, and ARTX.
Of 850 gliomas screened, 163 cases had midline glioma on MRI. Sufficient FFPE tissue was available for 123 cases (75%). H3 K27M mutation was identified in 18 of 123 cases (15%). All except one H3 K27M-mutant tumors were WHO grade III or IV on histology, while non-mutant tumors encompassed all four grades. The most common midline locations for H3 K27M-mutated tumors were midbrain (2/3; 67%), pons (4/11; 36%), and cerebellum (6/24; 25%). As compared to H3 K27M-wildtype tumors, there were no differences in age at diagnosis, sex, tumor grade, contrast enhancement on MRI, extent of resection, or treatment received. In this cohort, median survival was longer for patients with H3 K27M-mutated tumors (n = 18; 17.6 months) compared with high-grade wildtype tumors (n = 74; 7.7 months, p = 0.03).
H3 K27M mutations are common in midline gliomas in adults and can present in all midline locations. Survival comparison between H3 K27M-mutant and wildtype midline gliomas suggests that survival may be similar or possibly improved if the mutation is present.
H3 K27 突变，最常见于 H3F3A，在弥漫性中线胶质瘤中很常见。中线部位胶质瘤成人中这些突变的确切频率尚不清楚。本研究旨在确定该部位 H3 K27M 突变的发生率，并将其临床病理特征与未携带该突变的患者进行比较。
对 2007 年至 2017 年连续的胶质瘤病例进行筛查，以确定中线部位的胶质瘤。对所有可用组织进行 H3 K27M、IDH1 和 ARTX 的免疫组化检测。
在筛选的 850 例胶质瘤中，163 例 MRI 显示中线胶质瘤。123 例（75%）有足够的 FFPE 组织可供检测。在 123 例中，有 18 例（15%）发现 H3 K27M 突变。除了一个 H3 K27M 突变肿瘤外，所有肿瘤的组织学分级均为 III 级或 IV 级，而非突变肿瘤涵盖了所有四个分级。H3 K27M 突变肿瘤最常见的中线部位是中脑（2/3；67%）、脑桥（4/11；36%）和小脑（6/24；25%）。与 H3 K27M 野生型肿瘤相比，H3 K27M 突变肿瘤患者的诊断年龄、性别、肿瘤分级、MRI 对比增强、切除程度或治疗方法均无差异。在本队列中，H3 K27M 突变肿瘤患者（n=18）的中位生存期明显长于高级别野生型肿瘤患者（n=74；7.7 个月，p=0.03）。
H3 K27M 突变在成人中线胶质瘤中很常见，可发生在所有中线部位。H3 K27M 突变和野生型中线胶质瘤的生存比较表明，如果存在突变，生存可能相似或可能改善。
