The Genetic Alterations of Retinoblastoma Gene in Human Gliomas

ABSTRACT

The formation and malignant progression of gliomas are generally considered to undergo multistepped process like other tumors. Loss of 13q is implicated in the later stage of progression of gliomas. The retinoblastoma susceptibility gene(RB gene), located at the 13q14, is a prototypic tumor suppressor gene. Many kinds of tumors are noted to have mutations of the RB gene. To determine whether the loss of 13q is associated with RB gene or not, and to find the intragenic mutation of RB, we examined 28 gliomas for loss of heterozygosity(LOH) at the RB locus using a polymerase chain reaction-based restriction fragment length polymorphism(PCR-based RFLP) assay. We found LOH in 13 of 28(46%) gliomas. Eight of 12(67%) high-grade astrocytomas, 3 of 6(50%) differentiated astrocytomas showed LOH. And we also detected LOH in 1 of 2 anaplastic oligodendrogliomas and in 1 of 7(14%) differentiated oligodendrogliomas. When we classify them into low-grade and high-grade gliomas, 4 of 14(29%) low-grade gliomas, and 9 of 14(64%) high-grade gliomas showed LOH, PCR-SSCP analysis was performed on exon, 8, 14, 15, 16, 19, 20, 21, 22, 24 to find mutations in remaining allele, and one case of mobility shift was identified in glioblastoma multiforme which showed LOH in PCR-based RFLP study. Our results demonstrate that RB deletions are detected in both low-grade high-grade gliomas, and unlike the p53 gene, genetic alterations of the RB gene in gliomas are mainly deletions rather than point mutations.