PDGFRA Gain in Low-Grade Diffuse Gliomas
PDGFRA Gain in Low-Grade Diffuse Gliomas
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低级别弥漫性胶质瘤中的 PDGFRA 增益
DOI：
10.1097/nen.0b013e31827c4b5b
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
Ohgaki H
中科院分区：
文献类型：
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作者：
Motomura K;Mittelbronn M;Paulus W;Brokinkel B;Keyvani K;Sure U;Wrede K;Nakazato Y,Tanaka Y;Nonoguchi N;Pierscianek D;Kim YH;Mariani L;Vital A;Perry A;Ohgaki H
具有前神经表达特征的胶质母细胞瘤的特征是频繁的IDH 1突变（即继发性胶质母细胞瘤的遗传标志）和PDGFRA（血小板衍生生长因子受体-α）扩增。IDH 1/2突变是弥漫性星形细胞瘤（世界卫生组织II级）的常见和早期遗传事件，是继发性胶质母细胞瘤的前体，但对PDGFRA扩增在这些肿瘤中的作用和时间知之甚少。我们通过定量聚合酶链反应评估了342例低级别弥漫性胶质瘤中PDGFRA的表达。166例弥漫性星形细胞瘤中有27例（16.3%）PDGFRA增加，明显高于少突胶质细胞瘤（115例中有3例[2.6%]，p < 0.0001）。使用我们实验室先前发表的数据进行的分析显示，PDGFRA增加与IDH 1/2突变（p = 0.018）或1 p/19 q丢失（p < 0.0001）之间呈负相关。绝大多数弥漫性星形细胞瘤显示IDH 1/2突变和/或PDGFRA增加（154/166 [93%]）。弥漫性星形细胞瘤PDGFRA基因突变患者的平均生存期为8.8 ± 1.6年，与IDH 1/2基因突变患者（7.8 ± 0.5年）或TP 53基因突变患者（7.6 ± 0.6年）相似，但明显长于MET基因突变患者（4.4 ± 0.7年）。6例弥漫性星形细胞瘤中PDGFRA/MET共扩增的双色荧光原位杂交结果显示，PDGFRA和MET在不同的肿瘤细胞群体中有典型的扩增。还观察到具有共扩增的肿瘤细胞，表明即使在弥漫性星形细胞瘤中也存在瘤内异质性。
Glioblastomas with a proneural expression signature are characterized by frequent IDH1 mutations (i.e. genetic hallmarks of secondary glioblastomas) andPDGFRA(platelet-derived growth factor receptor-α) amplification. Mutations inIDH1/2are frequent and early genetic events in diffuse astrocytomas (World Health Organization grade II), precursor to secondary glioblastomas, but little is known about the role and timing ofPDGFRAamplification in these tumors. We assessedPDGFRAgain in 342 low-grade diffuse gliomas by quantitative polymerase chain reaction. Gain inPDGFRAwas detected in 27 (16.3%) of 166 diffuse astrocytomas, significantly more frequent than in oligodendrogliomas (3 [2.6%] of 115, p < 0.0001). Analyses using previously published data from our laboratory showed an inverse correlation betweenPDGFRAgain andIDH1/2mutations (p = 0.018) or 1p/19q loss (p < 0.0001). The vast majority of diffuse astrocytomas showedIDH1/2mutations and/orPDGFRAgain (154 [93%] of 166). Mean survival of diffuse astrocytoma patients withPDGFRAgain was 8.8 ± 1.6 years, similar to that withIDH1/2mutations (7.8 ± 0.5 years) or TP53 mutations (7.6 ± 0.6 years) but significantly longer than those with MET gain (4.4 ± 0.7 years). Dual-color fluorescence in situ hybridization in 6 diffuse astrocytomas withPDGFRA/MET co-gain identified by quantitative polymerase chain reaction revealed thatPDGFRAand MET were typically amplified in different tumor cell populations. Tumor cells with coamplification were also focally observed, suggesting intratumoral heterogeneity, even in diffuse astrocytomas.