Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.
Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.
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DOI：
10.1056/nejmoa1407279
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发表时间：
2015-06-25
期刊：
影响因子：
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通讯作者：
Jenkins RB
中科院分区：
文献类型：
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作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
浸润性胶质瘤的临床表现、治疗反应和预后的预测具有挑战性。在以前肿瘤生物学研究的基础上，我们使用三种改变定义了五个胶质瘤分子组：TERT启动子突变、IDH突变和染色体臂1 p和19 q共缺失（1 p/19 q共缺失）。我们检验了这样一个假设，即在基于这些特征的组内，肿瘤将具有相似的临床变量、获得性体细胞改变和种系变异。我们在1087例胶质瘤中对这些标志物中的每一个进行了阴性或阳性评分，并比较了五个主要分子组之间的获得性改变和患者特征。使用11，590个对照，我们评估了这些组与已知胶质瘤种系变异之间的关联。在615个II或III级胶质瘤中，29%具有所有三种改变（即，三阳性），5%有TERT和IDH突变，45%只有IDH突变，7%是三阴性，10%只有TERT突变; 5%有其他组合。在472例IV级胶质瘤中，不到1%为三阳性，2%有TERT和IDH突变，7%只有IDH突变，17%为三阴性，74%只有TERT突变。诊断时的平均年龄在仅IDH突变的胶质瘤患者中最低（37岁），在仅TERT突变的胶质瘤患者中最高（59岁）。分子组与II级或III级胶质瘤患者的总生存率独立相关，但与IV级胶质瘤患者无关。这些分子组与特定的种系变异相关。根据三种肿瘤标记物将胶质瘤分为五个主要组。各组的发病年龄、总生存期以及与生殖系变异的相关性不同，这意味着它们具有不同的发病机制。
The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants. Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triplepositive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants. Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis.