5 ' CpG island methylation of p16 is associated with absence of p16 expression in glioblastomas

Recent evidence shows that transcriptional silencing as a consequence of hy permethylation of CpG islands is an important mechanism in the inactivation of p16(INK4a) tumor suppressor gene. This study is designed to clarify the significance of p16(INK4a) hypermethylation in 23 cases of glioblastomas ( GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immun ostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylat ion cases showed complete loss of immunoreactivity and only one (7%) case r etained immunoreactivity. Among 9 methylation-negative cases, 4 were immuno negative, which might be related to mutations or deletions other than hyper methylation. The most significant finding was that of 17 cases with immunon egativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p1 6 hypermethylation may be one of the major mechanisms of tumorigenesis of G BMs and the results between the methylation specific-PCR study and p16 immu nostaining had a good correlation.