Allelic mutation on chromosome I 9 has previously been reported as a frequent genetic event in human glial tumors. In an effort to localize specific regions of importance on this chromosome better, I 3 highly polymorphic genetic markers distributed along the length of chromosome I9 were used for evaluation of loss of heterozygosity (LOH) and microsatellite instability in a total of I00 brain tumors, including 75 astrocytomas (55 grade 4; 7 grade 3; 5 grade 2; 6 grade I ; and 2 other), I7 oligodendrogliomas (I grade 4; 5 gradle 3; I0 grade 2; and I grade I), and 8 mixed oligoastrocytomas (MOA) (3 grade 4; 2 grade 3; and 3 grade 2). No microsatellite expansion was observed in these glial tumors for any of the chromosome I 9 loci examined. LOH for loci on chromosome I 9 was detected in 23/74 informative astrocytomas (3 I %), I I / I7 oligodendrogliomas (65%), and 3/8 MOA (38%). Partial deletion of chromosome 19 occurred more frequently (31/37 cases) than did loss of one whole copy of the chromosome, and a morphology-specific pattern of LOH was observed. In I U I4 (86%) instances of chromosome I 9 deletion in oligodendrogliomas and MOA, the 19q arm showed LOH, whereas the 19p arm showed no loss for all informative loci. Conversely, in 17/23 (74%) instances of chromosome I 9 deletion in astrocytomas, the I9p arm showed LOH, whereas the 19q arm showed no 10:~s for one or more loci. Thus, loss of 19q and retention of I9p are strongly associated with oligodendroglioma and MOA, whereas loss of I9p and retention of distal 19q is associated with astrocytoma. These data indicate that two or more tumor suppressor genes may reside on chromosome 19, one on I9p important in the development of astrocytomas, and one on 19q important in oligodendrogliomas and MOA. Genes Chromosom Cancer 12277-282 (1995).