Pollack Ian F, Hamilton Ronald L, Sobol Robert W, Nikiforova Marina N, Lyons-Weiler Maureen A, LaFramboise William A, Burger Peter C, Brat Daniel J, Rosenblum Marc K, Holmes Emiko J, Zhou Tianni, Jakacki Regina I
Department of Neurosurgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Childs Nerv Syst. 2011 Jan;27(1):87-94. doi: 10.1007/s00381-010-1264-1. Epub 2010 Aug 20.
Recent studies have demonstrated a high frequency of IDH mutations in adult "secondary" malignant gliomas arising from preexisting lower grade lesions, often in young adults, but not in "primary" gliomas. Because pediatric malignant gliomas share some molecular features with adult secondary gliomas, we questioned whether a subset of these tumors also exhibited IDH mutations.
We examined the frequency of IDH mutations, using real-time polymerase chain reaction and sequencing analysis, in a cohort of 43 pediatric primary malignant gliomas treated on the Children's Oncology Group ACNS0423 study. The relationship between IDH mutations and other molecular and clinical factors, and outcome, was evaluated.
IDH1 mutations were observed in 7 of 43 (16.3%) tumors; no IDH2 mutations were observed. A striking age association was apparent in that mutations were noted in 7 of 20 tumors (35%) from children ≥14 years, but in 0 of 23 (0%) younger children (p = 0.0024). No association was observed with clinical factors other than age. One-year event-free survival was 86 ± 15% in the IDH-mutated group versus 64 ± 8% in the non-mutated group (p = 0.03, one-sided logrank test). One-year overall survival was 100% in patients with mutations versus 81 ± 6.7% in those without mutations (p = 0.035, one-sided logrank test).
IDH1 mutations are common in malignant gliomas in older children, suggesting that a subset of these lesions may be biologically similar to malignant gliomas arising in younger adults and may be associated with a more favorable prognosis.
近期研究表明，在由先前存在的低级别病变发展而来的成人“继发性”恶性胶质瘤中，异柠檬酸脱氢酶（IDH）突变频率较高，这些病变常见于年轻成人，而在“原发性”胶质瘤中则不然。由于儿童恶性胶质瘤与成人继发性胶质瘤具有一些分子特征，我们不禁要问，这些肿瘤中是否有一部分也存在IDH突变。
我们采用实时聚合酶链反应和测序分析，对儿童肿瘤学组ACNS0423研究中治疗的43例儿童原发性恶性胶质瘤队列进行IDH突变频率检测。评估IDH突变与其他分子和临床因素以及预后之间的关系。
43例肿瘤中有7例（16.3%）检测到IDH1突变；未观察到IDH2突变。年龄与突变之间存在显著关联，14岁及以上儿童的20例肿瘤中有7例（35%）检测到突变，而23例年幼儿童中未检测到突变（p = 0.0024）。除年龄外，未观察到与其他临床因素的关联。IDH突变组的1年无事件生存率为86±15%，未突变组为64±8%（p = 0.03，单侧对数秩检验）。突变患者的1年总生存率为100%，未突变患者为81±6.7%（p = 0.035，单侧对数秩检验）。
IDH1突变在大龄儿童的恶性胶质瘤中常见，提示这些病变中的一部分在生物学上可能类似于年轻成人发生的恶性胶质瘤，且可能与更有利的预后相关。
