LOSS OF HETEROZYGOSITY ANALYSIS OF CHROMOSOME-9, CHROMOSOME-10 AND CHROMOSOME-17 IN GLIOMAS IN FAMILIES

Background: Studies of sporadic malignant gliomas have identified stru ctural abnormalities in a number of chromosomal regions, especially lo sses of DNA on 9p, 10 and 17p. Purpose: We undertook the following mol ecular analysis in families with glioma to determine the frequency of chromosomal losses in these regions and to test the utility of microsa tellite markers in demonstrating losses of heterozygosity. Methods: Ge nomic DNA was extracted from tumor tissue and venous blood from 20 pat ients with a family history of glioma, Dinucleotide repeat polymorphis ms (microsatellites) were analyzed by polymerase chain reaction to ass ess loss of constitutional heterozygosity (LOH) on 9p, 10 and 17p. Thr ee polymorphic markers on chromosome 9 (D9S104, D9S161, D9S165), one o n chromosome 10 (D10S209), and two on 17p (D17S786, D17S796) were used . Autoradiographic films were analyzed for LOH after radioactively lab elled polymerase chain reaction products were resolved on denaturing f ormamide-acrylamide gels. Results: Of 20 patients informative for at l east one of three chromosome 9 markers, 12 (60%) showed LOH at one or more loci; of 9 informative for the chromosome 10 marker, 4 (44%) show ed LOH; and of 16 informative for at least one of two chromosome 17 ma rkers, 7 (44%) showed LOH at one or both loci. These LOH rates do not include instances of tumor nullizygosity (0 - 35%) and therefore repre sent minimum frequencies of chromosomal losses at these loci. Conclusi ons: Microsatellite markers can be used to detect LOH in archival glio ma tissue, As in sporadic gliomas, frequent LOH was observed on 9p (9p 21-22), 10 and 17p, supporting the notion that these regions may harbo ur tumor suppressor genes important in glioma development. Further wor k will be required to determine whether the proportion of LOH in these chromosomal regions is higher in familial gliomas than sporadic ones, as might occur with an inherited suppressor gene conferring susceptib ility to gliomas in families.