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H3K27M和启动子突变是成人丘脑高级别胶质瘤手术病例中的不良预后因素。

H3K27M and promoter mutations are poor prognostic factors in surgical cases of adult thalamic high-grade glioma.

作者信息

Osada Yoshinari, Saito Ryuta, Shibahara Ichiyo, Sasaki Keisuke, Shoji Takuhiro, Kanamori Masayuki, Sonoda Yukihiko, Kumabe Toshihiro, Watanabe Mika, Tominaga Teiji

机构信息

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Department of Neurosurgery, Kitasato University Graduate School of Medicine, Kanagawa, Japan.

出版信息

Neurooncol Adv. 2021 Feb 28;3(1):vdab038. doi: 10.1093/noajnl/vdab038. eCollection 2021 Jan-Dec.

Abstract

BACKGROUND

Thalamic high-grade gliomas (HGGs) are rare tumors with a dismal prognosis. H3K27M and telomerase reverse transcriptase promoter () mutations reportedly contribute to poor prognoses in HGG cases. We investigated the outcomes of surgically treated adult thalamic HGGs to evaluate the prognostic significance of H3K27M and mutations.

METHODS

We retrospectively analyzed 25 adult patients with thalamic HGG who underwent maximum surgical resection from January 1997 to March 2020. The histological and molecular characteristics, progression-free survival (PFS), and overall survival (OS) of the patients were compared. For molecular characteristics, target sequencing was used to determine the , , and mutations.

RESULTS

H3K27M mutations were detected in 12/25 (48.0%) patients. mutations were not detected in H3K27M-mutant gliomas but were detected in 8/13 (61.5%) of H3 wild-type gliomas. Although it was not significant, H3K27M-mutant gliomas tended to have a shorter PFS (6.7 vs 13.1 months; = .2928) and OS (22.8 vs 24.4 months; = .2875) than H3 wild-type gliomas. Moreover, the prognosis of -mutant gliomas was as poor as that of H3K27M-mutant gliomas. Contrary, 5 gliomas harboring both H3 and wild-type showed a better median PFS (59.2 vs 6.4 months; = .0456) and OS (71.8 vs 24.4 months; = .1168) than those harboring H3K27M or mutations.

CONCLUSIONS

-mutant gliomas included in the H3 wild-type glioma group limited patient survival as they exhibited an aggressive course similar to H3K27M-mutant gliomas. Comprehensive molecular work-up for the H3 wild-type cases may further confirm this finding.

摘要

背景

丘脑高级别胶质瘤(HGGs)是罕见肿瘤,预后不佳。据报道,H3K27M和端粒酶逆转录酶启动子()突变会导致HGG病例预后不良。我们研究了手术治疗的成人丘脑HGG的预后,以评估H3K27M和突变的预后意义。

方法

我们回顾性分析了1997年1月至2020年3月期间接受最大程度手术切除的25例成人丘脑HGG患者。比较了患者的组织学和分子特征、无进展生存期(PFS)和总生存期(OS)。对于分子特征,采用靶向测序来确定、和突变。

结果

在12/25(48.0%)的患者中检测到H3K27M突变。在H3K27M突变型胶质瘤中未检测到突变,但在8/13(61.5%)的H3野生型胶质瘤中检测到突变。虽然差异不显著,但H3K27M突变型胶质瘤的PFS(6.7个月对13.1个月; = 0.2928)和OS(22.8个月对24.4个月; = 0.2875)倾向于比H3野生型胶质瘤短。此外,突变型胶质瘤的预后与H3K27M突变型胶质瘤一样差。相反,5例同时具有H3和野生型特征的胶质瘤的中位PFS(59.2个月对6.4个月; = 0.0456)和OS(71.8个月对24.4个月; = 0.1168)比具有H3K27M或突变的胶质瘤更好。

结论

H3野生型胶质瘤组中的突变型胶质瘤限制了患者的生存,因为它们表现出与H3K27M突变型胶质瘤相似的侵袭性病程。对H3野生型病例进行全面的分子检查可能会进一步证实这一发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/054a/8117440/dad831b39956/vdab038f0001.jpg

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