CDKN2A/p16 inactivation in the prognosis of oligodendrogliomas

The cell-cycle regulator p16 inhibits the complex cdk4-cyclin DI and contro ls G1-S transition. In human tumors, p16 inactivation is often accomplished by homozygous deletion (HD) of its encoding gene, CDKN2A, Methylation of t he 5' CpG island promoter has been proposed as an alternative mechanism of inactivation. Expression of p16, CDKN2A HD and 5' CDKN2A CpG island methyla tion was studied in 25 oligodendrogliomas by immunohistochemistry and PCR a mplification, Ten oligodendrogliomas were p16-immunonegative, and CDKN2A HD was determined in 8 of these cases. in the 2 immunonegative cases without HD, no CpG island methylation was found, The absence of CpG island methylat ion in the p16-immunonegative cases without HD suggests either non-genetic regulation of p16 or different genetic changes, CDKN2A HD did not correlate with histological grading (p = n.s.); however, it showed a correlation wit h survival (p = 0.03), supporting an important role of CDKN2A in the progno sis of oligodendrogliomas. (C) 2000 Wiley-Liss, Inc.