Cytogenetics and molecular genetics of malignant gliomas

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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.