Investigation of Morphological Characteristics and Genetic Aberration in Gliomas Using Microsatellite Markers

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The investigation was performed to establish the correlation between morphological characteristics and the genetic aberration in human gliomas. DNA from gliomas were amplified by polymerase chain reaction to detect loss of heterozygosity (LOH) at 33 microsatellite loci on chromosomes 9,10,17 and 22. The molecular genetic data were compared with immunohistochemistry performed with antibodies to glial fibrillary acidic protein (GFAP), MIB-1 and p53 protein and also with patient survival. Aberration of chromosome 9 was evidenced in 50% of imformative loci in malignant gliomas. Aberration of chromosome 10 was also evidented in 39.7% of the imformative loci in glioblastomas. Moreover, aberrations of chromosome 17 and 22 were rrelatively higher in 9.5%, 20.0% of the imformative loci, respectively, even in benign gliomas. LOH at D22S300 (22q12.1-q13.1) was exclusively seen (80%) in glioblastomas. LOH at 10q22-25 was consistently recognized in glioblastomas after recurrence from astrocytomas or anaplastic astrocytomas suggesting this area is closely relalated with most malignant progression in gliomas. The allelic status of D17S795 (17q21.2) in all informative instances were concordant with GFAP immunoreactivity (P<0.01 ; Fisher's test). Furthermore, the inter-chromosomal relationship disclosed a close correlation between the presence of frequent LOH in chromosome 17 or 22 and the occurrence of LOH in the other 3 chromosomes (R=0.601 ; P<0.01 ; Stepwise regression) suggesting the possible involvement of chromosome 17 and 22 in causing genomic instability. A trend of inverse relationship between the time of recurrence and the presence of LOH on chromosome 10 in anaplastic astrocytoma patients was seen. However, correlation between the presence or absence of LOH and patient survival was not apparent in cases of glioblastomas. The findings underscores the diverse and 'multi-chromosome based' nature of astrocytic tumors.