IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas.
IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas.
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DOI：
10.18632/oncotarget.4497
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发表时间：
2015-10-06
期刊：
影响因子：
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通讯作者：
Giannini C
中科院分区：
文献类型：
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作者：
Leeper HE;Caron AA;Decker PA;Jenkins RB;Lachance DH;Giannini C
表观遗传学、遗传学和分子生物学研究已经确定了弥漫性胶质瘤的几个诊断和预后标志物。它们对于评价WHO II级神经胶质瘤的重要性还有待具体描述。我们分析了159例WHO II级少突胶质细胞瘤、少突星形细胞瘤和星形细胞瘤（2003-2012）患者的标志物，包括IDH突变（IDHmut）、1 p19 q共缺失（1 p19 qcodel）、ATRX表达缺失（ATRX缺失）和p53过表达，以及预后。在141例（91%）IDHmut非编码肿瘤中发现IDHmut，在64例（87%）IDHmut非编码肿瘤中发现ATRX丢失（p = 0.003）。所有共缺失的肿瘤（n = 66）均为IDHmut。鉴定了四个亚组：IDHmut-codel，66（43%）; IDHmut-noncodel-ATRX丢失，60（39%）; IDHmut-noncodel-ATRXwt，9（6%）; IDHwt，14（9%）。4组之间的中位生存期显著不同（p = 0.038），特别是IDHmut-codel（中位生存期15.6年）与其余3组相比（p = 0.025）。组织学生存率无显著性差异。总体（OS），但非无进展（PFS），生存期显著长于肉眼全切除术与仅活检（p = 0.042）。次全切除患者的预后与仅活检患者无显著差异。在这些统一治疗的患者中，OS远远超过PFS，特别是在1 p/19 q共缺失的患者中。对于WHO II级弥漫性胶质瘤，使用1 p/19 qcodel、IDHmut和ATRX丢失的分子分类更准确地预测结果，并应纳入神经病理学评估。
Epigenetic, genetic, and molecular studies have identified several diagnostic and prognostic markers in diffuse gliomas. Their importance for evaluating WHO grade II gliomas has yet to be specifically delineated. We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003–2012). IDHmut was found in 141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors (p = 0.003). All codeleted tumors (n = 66) were IDHmut. Four subgroups were identified: IDHmut-codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt, 9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different (p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared to the remaining 3 groups (p = 0.025). Survival by histology was not significant. Overall (OS), but not progression-free (PFS), survival was significantly longer with gross total resection vs. biopsy only (p = 0.042). Outcomes for patients with subtotal resection were not significantly different from those with biopsy only. Among these uniformly treated patients, OS far exceeds PFS, particularly in those with 1p/19q codeletion. For WHO grade II diffuse glioma, molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately predicts outcome and should be incorporated in the neuropathologic evaluation.