Molecular definition of chromosome translocations involving 10q24 and 19q13 in human malignant glioma cells.

Loss of heterozygosity (LOH) analysis has repeatedly implicated the 10q24-26 region as the site of tumor suppressor genes involved in the development of malignant human gliomas. However, deletions of this kind are generally too big to pinpoint the critical genes involved. On the other hand, chromosome translocations frequently interrupt genes important in the development of the phenotype. We have screened a series of cell lines and cultures from primary human brain tumors for translocations involving chromosomes 10 and 19 by using fluorescence in situ hybridization (FISH) and chromosome-specific paints. The T98G cell line carries an apparently reciprocal t(10;19)(q24;q13) translocation, the breakpoints on chromosomes 10 and 19 occurring in a region frequently showing LOH in gliomas as well as oligodendrogliomas and astrocytomas. One glioblastoma tumor, CCF 4, also showed a subtle translocation of chromosome 10 material into the long arm of chromosome 11. FISH analysis of these rearrangements showed that the chromosome 10-specific yeast artificial chromosome (YAC) 912C7 spans the translocation breakpoint in T98G cells and is also present in the material translocated from chromosome 10 in tumor CCF 4. The translocation breakpoint in 19q13 in T98G occurs within a 500-kb region of YAC 751E12. These translocation breakpoints are within the regions showing frequent LOH in brain tumors and provide a more refined tool for the identification of genes in this region involved in tumorigenesis.