Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan.
Neurosurgery. 2011 Jan;68(1):206-12. doi: 10.1227/NEU.0b013e3181fd2c2e.
Reports of genetic analyses on pediatric gliomas are few, and those tumors have been far less characterized than adult gliomas.
To characterize the genetic and biological features of pediatric gliomas.
We investigated 23 pediatric nonependymal, nonpilocytic gliomas for chromosomal copy number aberrations (CNAs) by comparative genomic hybridization (CGH), mutations of isocitrate dehydrogenase (IDH) genes by direct sequencing, and proliferative activity and expression of O-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry.
The most frequent CNA was single-copy gain of chromosome 1q, with 10 of 20 successfully investigated tumors showing the abnormality (50%). Other CNAs detected by CGH included gain on 7q (+7q) in 6, +9q in 5, +17q in 5, and + 7p in 4 cases. Gain of entire chromosome 7 was rare (2 cases), and codeletion of 1p and 19q was not detected. Gain of 1q was significantly predictive for shorter progression-free survival (PFS) and overall survival (OS), and even more closely associated with poor clinical outcome than histological grade (P = .0009 for PFS, P = .003 for OS by 1q status; P = .004 for PFS, P = .035 for OS by high-grade vs low-grade). Gain of 1q was also significantly correlated with proliferative activity (P = .0002), and tumors with 1q gain showed a trend toward higher MGMT expression (P = .27). Mutation of IDH1 gene was detected in only 2 of 17 tumors successfully analyzed.
Single copy gain of 1q is associated with biological features of pediatric gliomas, and is a negative prognostic marker in patients with those tumors.
有关小儿神经胶质瘤的遗传分析报告很少，而且这些肿瘤的特征远不如成人神经胶质瘤那样明显。
描述小儿神经胶质瘤的遗传和生物学特征。
我们通过比较基因组杂交（CGH）检测了 23 例非室管膜、非毛细胞型小儿神经胶质瘤的染色体拷贝数异常（CNAs），直接测序检测异柠檬酸脱氢酶（IDH）基因突变，免疫组织化学法检测 O-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）的增殖活性和表达。
最常见的 CNA 是 1 号染色体单拷贝增益，在 20 例成功检测的肿瘤中有 10 例（50%）出现异常。CGH 检测到的其他 CNA 包括 6 例 7q 获得（+7q），5 例 9q 获得，5 例 17q 获得和 4 例 7p 获得。整条 7 号染色体获得很少见（2 例），未检测到 1p 和 19q 的缺失。1q 获得与较短的无进展生存期（PFS）和总生存期（OS）显著相关，甚至比组织学分级更密切地与不良临床结果相关（PFS 时 1q 状态为 0.0009，OS 时为 0.003，P = 0.004；PFS 时高级别与低级别比较为 0.004，OS 时高级别与低级别比较为 0.035）。1q 获得与增殖活性显著相关（P = 0.0002），并且 1q 获得的肿瘤表现出 MGMT 表达升高的趋势（P = 0.27）。在 17 例成功分析的肿瘤中仅检测到 2 例 IDH1 基因突变。
1q 单拷贝获得与小儿神经胶质瘤的生物学特征相关，并且是此类肿瘤患者的预后不良标志物。
