FREQUENT DELETION AND 5'-CPG ISLAND METHYLATION OF THE P16 GENE IN PRIMARY MALIGNANT-LYMPHOMA OF THE BRAIN

A total of 10 primary malignant lymphomas of the brain were examined f or deletion, mutation, and 5' CpG island methylation of the p16 gene, which is a candidate tumor suppressor gene with CDK-inhibitory functio n. In Southern blot analysis, pld gene deletion was suggested in nine cases, homozygously (five cases) or hemizygously (four cases). In the remaining one case, p16 gene deletion was not suggested. Although sing le-strand conformation polymorphism and nucleotide analyses suggested no mutations of the p16 gene in these cases, methylation analyses reve aled 5' CpG island methylation in three cases, of which two were those with presumed hemizygous deletion and one was that without deletion i n Southern blot analysis, Thus, p16 gene abnormality was detected in a ll 10 of the brain lymphomas examined, and in 8 of them, actual p16 ge ne inactivation was suggested by their homozygous deletion (5 cases) o r 5' CpG island methylation (3 cases). These findings suggest that p16 gene abnormality and inactivation are closely related to carcinogenes is in primary malignant lymphoma of the brain. The p15 gene, another c andidate tumor suppressor gene located in the vicinity of the p16 gene , to which it shows structural and functional similarity, was also pre sumed to be deleted similarly in most cases. Its methylation was seen in one case, the case without the methylated p16 gene.