Lossofdistinct regions ontheshort armofchromosome 17 associated withtumorigenesis ofhumanastrocytomas

Astrocytomas, including glioblastoma multi- forme, represent themostfrequent anddeadly primary neo- plasms ofthehumannervous system. Despite anumberof previous cytogenetic andoncogene studies primarily focusing onmalignant astrocytomas, theprimary mechanism oftumor initiation hasremained obscure. Theloss orinactivation of "tumor suppressor" genes arethought toplay afundamental role inthedevelopment ofmanyhumancancers. Thus, wehave analyzed astrocytomas ofvarious histological malignancy grades withpolymorphic DNAmarkers tosearch forspecific chromosomal deletions potentially pointing toloci containing tumorsuppressor genes. Lossofconstitutional heterozygosity indicating chromosomal loss ordeletions wasmostfrequently seen formarkers ontheshort armofchromosome 17in50% oftheinformative tumors (5of10informative cases) and, toa lesser extent, formarkers onchromosomes 1and10.Deletions onchromosome 17pwereseeninbothlow-grade andhigh- grade manantastrocytomas, suggesting thatthis chromo- somemaycontain atumorsuppressor gene associated with the early events intumorigenesis. Thecommonregion ofdeletions ontheshort armofchromosome 17is,therefore, dearly distinct fromthegenecausing vonRecklinghausen neurofibro- matosis (NF1), atumorsyndrome associated withglial tumors that mapstothelong armofchromosome 17.Thesearch for progressively smaller deletions onchromosome 17pinastro- cytomas maybethewaytoclone andcharacterize this locus, thus leading toinsights into normal andabnormal growth and differentiation ofgial cells.