CDKN2A/p16 inactivation in the prognosis of oligodendrogliomas.
The cell-cycle regulator p16 inhibits the complex cdk4-cyclin D1 and controls G1-S transition. In human tumors, p16 inactivation is often accomplished by homozygous deletion (HD) of its encoding gene, CDKN2A. Methylation of the 5' CpG island promoter has been proposed as an alternative mechanism of inactivation. Expression of p16, CDKN2A HD and 5' CDKN2A CpG island methylation was studied in 25 oligodendrogliomas by immunohistochemistry and PCR amplification. 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 methylation 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 with survival (p = 0.03), supporting an important role of CDKN2A in the prognosis of oligodendrogliomas.
Bortolotto
S
S
Division of Neurology, Department of Neuroscience, University of Turin, Turin, Italy.
Chiadò-Piat
L
L
Cavalla
P
P
Bosone
I
I
Chiò
A
A
Mauro
A
A
Schiffer
D
D
D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002467:Cell Nucleus / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000737:chemistry; D017353:Gene Deletion; D019942:Genes, p16; D006720:Homozygote; D006801:Humans; D009837:Oligodendroglioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D016019:Survival Analysis
D019941:Cyclin-Dependent Kinase Inhibitor p16; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide