Different IDH Mutation and 1p/19q Codeletion Rates between Astrocytoma, Oligodendrocytoma and Mixed Gliomas

Jingchi Sun, Zhen Wang, Qiang Liu, Xinyong Huang, Zaihua Xu
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Abstract

Background: The mutations of isocitrate dehydrogenase (IDH-mt) and loss of chromosome 1p and 19q (1p/19q codeleltion) have been used in diagnosis of gliomas, especially in identification of oligodendrocytoma. We have performed and analyzed genetic detections with 3 types of gliomas diagnosed by morphological methods. Methods: The DNA extracted from tumor tissues of 136 patients with astrocytoma, oligodendrogliomas and mixed gliomas were subjected to fluorescence PCR capillary electrophoresis for detection of 1p and 19q codeletion and DNA sequencing for IDH mutations. The results were analyzed by SPSS 22.0 software with chi-square test for significant difference (p<0.05). Results: Among 136 patients, 77 cases (56.6%) were histopathologically diagnosed as astrocytoma (AA, WHO ), 11 (8.0%) as pure oligodendroglial tumors including both low-grade oligodendrogliomas (OA, WHO ) and anaplastic oligodendrogliomas (AOA, WHO ), and 48 (35.4%) as mixed glioma with the features of OA and AA in the same tumor tissue. The genetic detections have shown that 39 cases (28.7%) were with IDH mutations (37 IDH1-mt p.R132H and 2 IDH2-mt), and 47 (34.6%) with 1p/19q co-deletion. The significant differences of the IDH mt (p=0.008) and 1p/19q codeletion (p=0.011) were between 3 pathological types of astrocytoma, oligodendrogliomas and mixed glioms (p=0.008). In three glioma types, the rate of 1p/19q co-deletion was highest in the group of oligodendrogliomas (p=0.040). In 11 patients who were histopathologically diagnosed as oligodendroglioma, only 5 cases meet the WHO criterion that requires the presence of both 1p/19q codeletion and IDH1-mt or IDH2-mt. Conclusion: The rate of IDH mutations and 1p/19q codeletion is significantly different in three groups of gliomas, and highest in oligodendrogliomas. Some cases of oligodendrogliomas with only IDH mutation but without 1p/19q codeletion. Therefore, the genetic detections should be complemented for diagnosis of gliomas.
星形细胞瘤、少突胶质细胞瘤和混合胶质瘤中IDH突变和1p/19q编码率的差异
背景:异柠檬酸脱氢酶(IDH-mt)突变和染色体1p和19q缺失(1p/19q共缺失)已被用于胶质瘤的诊断,尤其是少突细胞瘤的鉴定。我们对3种形态学诊断的胶质瘤进行了基因检测并进行了分析。方法:从136例星形细胞瘤、少突胶质细胞瘤和混合胶质瘤患者的肿瘤组织中提取DNA,采用荧光PCR毛细管电泳检测1p和19q密码缺失,并对IDH突变进行DNA测序。采用SPSS 22.0软件进行统计学分析,差异有统计学意义(p<0.05)。结果:136例患者中,组织病理学诊断为星形细胞瘤(AA, WHO) 77例(56.6%),纯少突胶质细胞瘤11例(8.0%),包括低级别少突胶质细胞瘤(OA, WHO)和间变性少突胶质细胞瘤(AOA, WHO), 48例(35.4%)为同一肿瘤组织中具有OA和AA特征的混合胶质瘤。基因检测结果显示,39例(28.7%)存在IDH突变(37例IDH1-mt p.R132H和2例IDH2-mt), 47例(34.6%)存在1p/19q共缺失。星形细胞瘤、少突胶质细胞瘤和混合胶质瘤3种病理类型间IDH mt (p=0.008)和1p/19q编码(p=0.011)差异均有统计学意义(p=0.008)。在三种胶质瘤类型中,少突胶质细胞瘤组1p/19q共缺失率最高(p=0.040)。在11例组织病理学诊断为少突胶质细胞瘤的患者中,只有5例符合who的标准,即同时存在1p/19q密码缺失和IDH1-mt或IDH2-mt。结论:IDH突变率和1p/19q编码率在三组胶质瘤中差异有统计学意义,以少突胶质细胞瘤最高。一些少突胶质细胞瘤只有IDH突变,但没有1p/19q编码。因此,基因检测应作为胶质瘤诊断的补充。
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