REFINED DELETION MAPPING OF THE CHROMOSOME 19Q GLIOMA TUMOR-SUPPRESSOR GENE TO THE D19S412-STD INTERVAL

Allelic loss of chromsome 19q occurs frequently in malignant gliomas, suggesting the presence of a chromosome 19q glioma tumor suppressor ge ne, Deletion mapping studies have delineated a 3.5 Mb candidate region between D19S219 and HRC, Cloned sequences from the proximal 425 kb of this interval, however, have not shown tumor-specific alterations, To refine the location of the tumor suppressor gene further, we conducte d loss of heterozygosity studies on 191 malignant gliomas using nine P CR-based polymorphisms, These included the previously identified and p hysically mapped markers D19S219, DM, D19S112, HRC and the recently ph ysically mapped polymorphisms at D19S412, STD, D19S596 and GYS. In add ition, we isolated a novel microsatellite polymorphism that maps 400 k b telomeric to D19S112, Oligodendroglial tumors showed frequent loss o f heterozygosity in all grades, and typically displayed allelic loss a t all studied markers, Astrocytomas, however, showed frequent loss pri marily in anaplastic astrocytomas and displayed deletion breakpoints w ithin the candidate region, Deletion mapping revealed a minimal region of overlap between D19S412 and STD, a distance of 900 kb, These data suggest that the D19S412-STD interval represents the most likely locat ion for a chromsome 19q glioma tumor suppressor gene involved in astro cytoma, and perhaps oligodendroglioma, tumorigenesis.