Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Center for Precision Medicine, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea.
Brain Tumor Pathol. 2021 Jan;38(1):4-13. doi: 10.1007/s10014-020-00378-8. Epub 2020 Sep 29.
H3F3A G34 (H3.3 G34)-mutant high-grade gliomas (HGG) are rare, and newly recognized infiltrating gliomas of the cerebral hemisphere. Here, we report the clinicopathological and molecular characteristics of four H3.3 G34-mutant gliomas in terms of its biological behavior compared to those of glioblastomas (GBMs) and H3 K27M-mutant diffuse midline gliomas (DMGs) of our hospital. The median age of the four patients with H3.3 G34 HGG was 44.5 years (14-66 years). Three patients had tumors in the cerebral hemisphere, whereas one patient had synchronous double tumors in the cerebral hemisphere and posterior fossa. All these tumors were high-grade glioma, but neither microvascular proliferation nor necrosis. They displayed uniform genetic and epigenetic signatures; ATRX-mutant, MGMT promoter-methylated, Olig2-negative, but IDH- and TERT promoter-wildtype. The median survival rate of H3.3 G34-mutant HGGs, IDH-was 23.5 months. In conclusion, H3.3 G34-mutant gliomas were unique HGGs with uniform genetic and epigenetic abnormalities, which suggested a single phylogenic origin. The median survival of H3.3 G34-mutant HGGs was better than those of IDH-wildtype GBMs and H3 K27M-mutant DMGs, but worse than that of IDH-mutant GBM. The tumor-infiltrating area and resectability may be the crucial parameters for the prognosis of the patients.
H3F3A G34（H3.3 G34）-突变型高级别胶质瘤（HGG）较为罕见，属于新认识的大脑半球浸润性胶质瘤。本研究报道了 4 例 H3.3 G34 突变型胶质瘤的临床病理和分子特征，将其生物学行为与本医院的胶质母细胞瘤（GBM）和 H3 K27M 突变型弥漫性中线胶质瘤（DMG）进行了比较。4 例 H3.3 G34 突变型 HGG 患者的中位年龄为 44.5 岁（14-66 岁）。3 例患者肿瘤位于大脑半球，1 例患者大脑半球和后颅窝同时存在 2 个肿瘤。所有肿瘤均为高级别胶质瘤，但无微血管增生或坏死。它们显示出一致的遗传和表观遗传特征；ATRX 突变，MGMT 启动子甲基化，Olig2 阴性，但 IDH 和 TERT 启动子野生型。H3.3 G34 突变型 HGG、IDH 患者的中位总生存期为 23.5 个月。总之，H3.3 G34 突变型胶质瘤是具有一致遗传和表观遗传异常的独特的高级别胶质瘤，提示单一的系统发生起源。H3.3 G34 突变型 HGG 的中位生存时间优于 IDH 野生型 GBM 和 H3 K27M 突变型 DMG，但比 IDH 突变型 GBM 差。肿瘤浸润区域和可切除性可能是患者预后的关键参数。
