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 hypermethylation of CpG islands is an important mechanism in the inactivation of p16INK4 tumor suppressor gene. This study is designed to clarify the significance of p16INK4 hypermethylation in 23 cases of glioblastomas (GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immunostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylation cases showed complete loss of immunoreactivity and only one (7%) case retained immunoreactivity. Among 9 methylation-negative cases, 4 were immunonegative, which might be related to mutations or deletions other than hypermethylation. The most significant finding was that of 17 cases with immunonegativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p16 hypermethylation may be one of the major mechanisms of tumorigenesis of GBMs and the results between the methylation specific-PCR study and p16 immunostaining had a good correlation.
Park
S H
SH
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Jung
K C
KC
Ro
J Y
JY
Kang
G H
GH
Khang
S K
SK
D020121:5' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D016375:Antisense Elements (Genetics); D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000502:physiology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing / Q000502:physiology; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D020121:5' Untranslated Regions; D016375:Antisense Elements (Genetics); D019941:Cyclin-Dependent Kinase Inhibitor p16