Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas
Isocitrate Dehydrogenase 1 Codon 132 Mutation Is an Important Prognostic Biomarker in Gliomas
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DOI：
10.1200/jco.2009.21.9832
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发表时间：
2009-09-01
影响因子：
45.3
通讯作者：
Delattre, Jean-Yves
中科院分区：
文献类型：
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作者：
Sanson, Marc;Marie, Yannick;Delattre, Jean-Yves
异柠檬酸脱氢酶（IDH 1）基因第132位密码子突变在胶质母细胞瘤中的发生率为12（100例2级、121例3级和183例4级胶质瘤），并与组织学、基因组谱、结果共发现155例132位密码子突变，其中131例为Arg 132 His（88.5%）。IDH 1基因突变与胶质瘤的分级呈负相关，2级胶质瘤中IDH 1基因突变率为77%，3级胶质瘤中IDH 1基因突变率为55%，4级胶质瘤中IDH 1基因突变率为6%（P < 10（-15））。IDH 1突变与1 p19 q共缺失基因型（P < 10（-14））和MGMT甲基化状态（P <0.001）密切相关，但与EGFR扩增（P < 10（-15））和10号染色体缺失（P < 10（-15））相互排斥。IDH 1突变的存在与2级（分别为150.9 vs60.1个月; P = 0.01）、3级（分别为81.1 vs19.4个月; P <0.001）和4级胶质瘤（分别为27.4 vs 14个月; P <0.01）的预后更好相关。在校正了分级、年龄、MGMT状态、基因组特征和治疗后，多变量分析证实IDH 1突变是一个独立的有利预后标志物（风险比= 0.297; 95% CI，0.157至0.564，P = .00021）结论IDH 1基因第132位密码子突变与肿瘤的基因组学特征密切相关，是判断肿瘤预后的重要指标。2 - 4级胶质瘤的标志物。
PurposeUnexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 12% of glioblastomas.Patients and MethodsIDH1 codon 132 sequencing was performed in a series of 404 patients with glioma (100 grade 2, 121 grade 3, and 183 grade 4 gliomas) and correlated with histology, genomic profile, methylguanyl methyltransferase (MGMT) promoter methylation status, and outcome.ResultsA total of 155 codon 132 mutations were found, of which 131 were Arg132His (88.5%). The IDH1 mutation was inversely correlated with grade, affecting 77% of grade 2, 55% of grade 3, and 6% of grade 4 gliomas (P < 10(-15)). The IDH1 mutation was tightly associated with a 1p19q codeleted genotype (P < 10(-14)) and an MGMT methylated status (P < .001) but mutually exclusive with EGFR amplification (P < 10(-15)) and loss of chromosome 10 (P < 10(-15)). The presence (v absence) of IDH1 mutation was associated with a better outcome in grade 2 (150.9 v 60.1 months, respectively; P = .01), grade 3 (81.1 v 19.4 months, respectively; P < .001), and grade 4 gliomas (27.4 v 14 months, respectively; P < .01). After adjustment for grade, age, MGMT status, genomic profile, and treatment, multivariate analysis confirmed that IDH1 mutation was an independent favorable prognostic marker (hazard ratio = 0.297; 95% CI, 0.157 to 0.564, P = .00021).ConclusionThis study indicates that IDH1 codon 132 mutation is closely linked to the genomic profile of the tumor and constitutes an important prognostic marker in grade 2 to 4 gliomas.