未经辅助治疗的 IDH 突变星形细胞瘤的分子病史。

IF 5.8 2区 医学 Q1 CLINICAL NEUROLOGY
Brain Pathology Pub Date : 2024-10-30 DOI:10.1111/bpa.13300
Zhi-Feng Shi, Kay Ka-Wai Li, Johnny Sheung-Him Kwan, Nellie Yuk-Fei Chung, Sze-Ching Wong, Abby Wai-Yan Chu, Hong Chen, Danny Tat-Ming Chan, Ying Mao, Ho-Keung Ng
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引用次数: 0

摘要

高突变和恶性转化是替莫唑胺治疗 IDH 突变胶质瘤的潜在并发症。然而,对未接受替莫唑胺治疗的 IDH 突变低级别胶质瘤的自然病史研究其实并不多。我们从本医院回顾性检索了19例IDH突变、1p19q无编码2级星形细胞瘤患者的配对肿瘤,这些患者在原发切除和首次复发之间没有接受过替莫唑胺或放疗的中期辅助治疗。有两名患者获得了多次复发的组织,在切除最后一个标本之前,他们接受了放疗,但没有使用替莫唑胺。我们通过DNA甲基化分析、拷贝数变异(CNV)分析、靶向DNA测序、TERTp测序、ALT的FISH检测和选定的生物标记物,研究了这些低级别IDH突变星形细胞瘤的自然分子病史,这些肿瘤没有使用替莫唑胺的压力。复发的肿瘤大多级别较高(15/19 例患者),并具有原发肿瘤中不存在的新 CNV(17/19 例患者)。在复发的肿瘤中几乎没有发现新的突变。17/19(89.5%)例患者的肿瘤在复发时出现 CDKN2A 同源缺失、MYC 或 PDGFRA 局灶和非局灶增殖。没有出现高突变的病例。为两名多次复发患者的肿瘤构建的系统发生树表明,在没有替莫唑胺的压力下,他们的肿瘤演化过程中缺乏亚克隆的发展。总之,我们的研究表明,与替莫唑胺诱导的高突变现象相反,IDH 突变、1p19q 非缺失编码的 2 级星形细胞瘤在未接受替莫唑胺治疗的情况下,在肿瘤复发时获得了新的 CNV。这些发现加深了我们对 IDH 突变星形细胞瘤分子生活史的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The molecular history of IDH-mutant astrocytomas without adjuvant treatment.

Hypermutation and malignant transformation are potential complications arising from temozolomide treatment of IDH-mutant gliomas. However, the natural history of IDH-mutant low-grade gliomas without temozolomide treatment is actually under-studied. We retrieved retrospectively from our hospitals paired tumors from 19 patients with IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas where no interim adjuvant treatment with either temozolomide or radiotherapy was given between primary resections and first recurrences. Tissues from multiple recurrences were available from two patients and radiotherapy but not temozolomide was given before the last specimens were resected. We studied the natural molecular history of these low-grade IDH-mutant astrocytomas without pressure of temozolomide with DNA methylation profiling and copy number variation (CNV) analyses, targeted DNA sequencing, TERTp sequencing, FISH for ALT and selected biomarkers. Recurrences were mostly higher grades (15/19 patients) and characterized by new CNVs not present in the primary tumors (17/19 cases). Few novel mutations were identified in recurrences. Tumors from 17/19 (89.5%) patients showed either CDKN2A homozygous deletion, MYC or PDGFRA focal and non-focal gains at recurrences. There was no case of hypermutation. Phylogenetic trees constructed for tumors for the two patients with multiple recurrences suggested a lack of subclone development in their evolution when under no pressure from temozolomide. In summary, our studies demonstrated, in contrast to the phenomenon of temozolomide-induced hypermutation, IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas which had not been treated by temozolomide, acquired new CNVs at tumor recurrences. These findings improve our understanding of the molecular life history of IDH-mutant astrocytomas.

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来源期刊
Brain Pathology
Brain Pathology 医学-病理学
CiteScore
13.20
自引率
3.10%
发文量
90
审稿时长
6-12 weeks
期刊介绍: Brain Pathology is the journal of choice for biomedical scientists investigating diseases of the nervous system. The official journal of the International Society of Neuropathology, Brain Pathology is a peer-reviewed quarterly publication that includes original research, review articles and symposia focuses on the pathogenesis of neurological disease.
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