Cytogenetics and molecular genetics of malignant gliomas

人类最常见的中枢神经系统肿瘤来自大脑中的神经胶质细胞。多形性胶质母细胞瘤(GBM)是一种恶性程度最高的脑肿瘤，目前尚无法治愈。在这些肿瘤中，已有几种类型的遗传改变被报道，如基因扩增、染色体区域丢失和细胞遗传学异常。对20例原发于神经外胚层的人脑肿瘤进行了癌基因(erbB、Nmyc、c-myc或v-sis)的扩增检测，其中包括8例胶质瘤。在2个GBM中扩增了erbB，在另一个GBM中共扩增了N-myc和c-sis。此外，为了确定特定的染色体位点是否在GBM中丢失，我们使用针对人类染色体3、7、8.9.10.13和22的Wome多态DNA标记检测了5 GB&F中的杂合性丢失(LOH)。4个GBM在10号染色体上显示LOH，另一个在8号和22号染色体上同时显示LOH。。此外，对15例脑肿瘤(胶质瘤13例，畸胎瘤13例，神经母细胞瘤1例)进行了细胞遗传学分析。其中6例可分析恶性胶质瘤。其中3例CASCs涉及9号染色体，但涉及的每个断裂点并不常见。双重最小染色体(Dmins)和均一染色区(i-ISR)。在4例复发或恶性胶质瘤中检测到基因扩增的细胞遗传学标志。此外，I(17q)在恶性神经母细胞瘤中也被检测到。目前的结果表明ErbB扩增与胶质瘤的发生或侵袭性密切相关。同时也提示在10号染色体上存在一个与GBM发育有关的隐性基因。

The most common CNS neoplasms in humans are derived from glial cells in the brain. Glioblastoma multiform (GBM), the most malignant type of brain tumor, is at present incurable. In these tumors, several types of genetic alterations, such as gene amplification, loss of chromosomal regions and cytogenetic abnormalities have been reported. Amplification of oncogenes (erbB, Nmyc, c-myc or v-sis) were examined in 20 primary human brain tumors of neuroectodermal origin, including 8 GBMs. The erbB was amplified in 2 GBMS, and the N-myc and c-sis were coamplified in another GBM. Further, to determine whether specific chromosomal Ioci are lost in GBM, we examined loss of heterozygosity (LOH) in 5 GB&fs using Wome polymorphic DNA markers specific for human chromosomes 3, 7, 8.9.10.13 and 22. Four GBMs showed LOH on chromosome 10 and another showed simultancous LOH on chromosomes 8 and 22. . In addition, cytogenctic analysis was performed in 15 brain tumors (13 gliomas, I teratoma and I neurofibloma). Of them 6 malignant gliomas could be analyzed. Chromosomc 9 was involvcd in 3 cascs of them, although each breakpoint involved was not common. Doublc miinute chromosomes (dmins) and homogeneously staining region (I-ISR). which are cytogenetic hallmark of gene amplification, were detected in 4 recurrent or malignant gliomas. In addition i(17q)was detected in malignant neurofibloma.Present results indicate that erbb amplification is strongly associated with eumorgenesis or the aggressiveness of gliomas. and also suggest that a recessive gene involved in the development of GBM is present on chromosome 10.