2 TUMOR SUPPRESSIVE LOCI ON CHROMOSOME-10 INVOLVED IN HUMAN GLIOBLASTOMAS

A number of cytogenetic and molecular analyses have revealed very freq uent and extensive losses of regions of chromosome 10 in human gliobla stomas. Our recent studies have demonstrated that the transfer of a ch romosome 10 into human glioblastoma cells resulted in suppression of t heir transformed and tumorigenic phenotype. To localize the suppressiv e region further, we isolated and characterized certain hybrid cells t hat had undergone chromosomal rearrangements to yield hybrid cells ret aining only various regions of the inserted chromosome 10. One series of subclones showed the loss of the majority of the long arm of chromo some 10 (10q21-10qter) and regained the ability to grow under anchorag e-independent conditions, but the cells still failed to exhibit signif icant tumorigenicity in nude mice. Another set of subclones exhibited major deletions of large segments of the long arm of chromosome 10 (10 q21-q23; 10q26-qter), yet retained certain distal alleles associated w ith 10q24 to 10q26. These subclones were identical in their biological characteristics to the hybrids containing an intact chromosome 10, ex hibiting no growth in soft agarose or in nude mice. These results impl icate the presence of two independent phenotypicaily suppressive regio ns on chromosome 10 (10pter-q11 and 10q24-q26) that are involved in gl ioma progression. (C) 1995 Wiley-Liss, Inc.