No abstract

No abstract

A total of 10 glioma cell lines were examined for alterations of the p16, p15, p53 and p21 genes, which are tumor suppressor genes or candidates with direct or indirect CDK‐inhibitory functions. Genetic alterations (deletions or mutations) were frequently seen in the p16, p15 and p53 genes in these cell lines, but not in the p21 gene. When the states of the p16, p15 and p53 genes were compared among cell lines, all the cell lines showed abnormalities in at least 1 gene, often in 2 or 3 genes coincidentally, suggesting that dysfunction of these genes is closely related to glioma cell growth. Although alteration of all 3 genes was most frequent, there were cell lines having either p16/p15 or p53 or p16 and p53 gene alterations, suggesting that the time order of these genetic alterations was variable depending on the cell line. Among cell lines examined, one with homozygous p53 gene deletion seemed of particular practical value, since such a cell line might be useful in various studies, including investigation of the functions of various mutant p53 genes in the absence of heteromeric protein formation. On examination of the primary tumor tissues, the same alterations of the p16/p15 and p53 genes as detected in the cell lines were demonstrated in all 6 cases examined: p16/p15 gene deletion in 1, p16 gene mutation in 1 and p53 gene mutations in 5 cases. This suggested that the p16/p15 and the p53 gene alterations and their combinations in at least some glioma cell lines reflected those in the primary glioma tissues.

The p16 (MTS‐1) gene, a candidate tumor suppressor gene, was examined by means of Southern blot, PCR‐SSCP (polymerase chain reaction‐single‐strand conformation polymorphism) and nucleotide analyses in 5 cases of primary malignant lymphoma of the brain. By Southern blot analysis, the p16 gene was found to be deleted in at least 4 cases, homozygously (3 cases) or hemizygously (1 case). The p15 (MTS‐2) gene, another candidate tumor suppressor gene located in the vicinity of the p16 gene, to which it shows structural and functional similarity, was also found to be deleted in 4 cases. Our frequent detection (80%) of p16 and p15 gene deletions might suggest that these deletions are closely related to carcinogenesis in primary malignant lymphoma of the brain. SSCP and nucleotide analyses revealed no mutations of the p16 gene in any of the cases.