Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.
Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.
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DOI：
10.18632/oncotarget.588
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发表时间：
2012-07
期刊：
影响因子：
--
通讯作者：
Yan H
中科院分区：
文献类型：
--
作者：
Jiao Y;Killela PJ;Reitman ZJ;Rasheed AB;Heaphy CM;de Wilde RF;Rodriguez FJ;Rosemberg S;Oba-Shinjo SM;Nagahashi Marie SK;Bettegowda C;Agrawal N;Lipp E;Pirozzi C;Lopez G;He Y;Friedman H;Friedman AH;Riggins GJ;Holdhoff M;Burger P;McLendon R;Bigner DD;Vogelstein B;Meeker AK;Kinzler KW;Papadopoulos N;Diaz LA;Yan H
在胶质瘤的特定亚型中发现了关键染色质修饰物ATRX的突变以及CIC和FUBP1的突变，CIC和FUBP1是细胞生长的有效调节因素。胶质瘤是最常见的原发恶性脑瘤类型。然而，这些突变在许多亚型胶质瘤中的频率，以及它们与患者临床特征的关系，还知之甚少。在这里，我们分析了363个脑瘤中的这些基因座。ATRX突变在II-III级星形细胞瘤(71%)、少星形细胞瘤(68%)和继发性胶质母细胞瘤(57%)中经常发生，ATRX突变与IDH1突变和另一种端粒表型延长有关。CIC和FUBP1突变在少突胶质细胞瘤中常见(分别为46%和24%)，而在星形细胞瘤或少突胶质细胞瘤中很少(10%)。这一分析使我们能够在胶质瘤中定义两个高度复发的遗传特征：IDH1/ATRX(I-A)和IDH1/CIC/FUBP1(I-CF)。I-CF胶质瘤患者的中位总生存期(96个月)明显长于I-A胶质瘤患者(51个月)和未出现上述两种症状的患者(13个月)。基因特征区分了临床上不同的寡星形细胞瘤患者组，这通常是诊断上的一个挑战，并与临床结果的差异有关，即使在不同的肿瘤类型之间也是如此。除了提供关于胶质瘤潜在遗传变化的新线索外，该结果还具有直接的临床意义，提供了一个三方基因签名，可以作为传统胶质瘤分类的有用辅助工具，可能有助于预后、治疗选择和治疗试验设计。
Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequency of these mutations in many subtypes of gliomas, and their association with clinical features of the patients, is poorly understood. Here we analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II-III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas (57%), and ATRX mutations are associated with IDH1 mutations and with an alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in astrocytomas or oligoastrocytomas (<10%). This analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer median overall survival (96 months) than patients with I-A gliomas (51 months) and patients with gliomas that did not harbor either signature (13 months). The genetic signatures distinguished clinically distinct groups of oligoastrocytoma patients, which usually present a diagnostic challenge, and were associated with differences in clinical outcome even among individual tumor types. In addition to providing new clues about the genetic alterations underlying gliomas, the results have immediate clinical implications, providing a tripartite genetic signature that can serve as a useful adjunct to conventional glioma classification that may aid in prognosis, treatment selection, and therapeutic trial design.
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影响因子：
16.8
作者：
Iwase, Shigeki;Xiang, Bin;Ghosh, Sharmistha;Ren, Ting;Lewis, Peter W.;Cochrane, Jesse C.;Allis, C. David;Picketts, David J.;Patel, Dinshaw J.;Li, Haitao;Shi, Yang
通讯作者：
Shi, Yang
影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
DOI：
10.1038/modpathol.2009.114
发表时间：
2009-11
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.4
作者：
Kim, Young-Ho;Lachuer, Joel;Ohgaki, Hiroko
通讯作者：
Ohgaki, Hiroko
影响因子：
15.9
作者：
Ichimura K;Pearson DM;Kocialkowski S;Bäcklund LM;Chan R;Jones DT;Collins VP
通讯作者：
Collins VP