Loss of P16INK4 expression is frequent in high grade gliomas.
P16INK4 is a cell cycle regulator that specifically binds to and inactivates cyclin-dependent kinase 4 (CDK4). Its encoding gene (p16/CDKN2) maps to chromosome 9p21, a region that undergoes frequent loss of heterozygosity in a variety of human tumors. We have analyzed the p16/CDKN2 gene and its expression in a series of primary glioma samples. Although homozygous deletion or mutation of the p16/CDKN2 gene was uncommon in this series and P16INK4 protein was detectable in all grade II tumors, it was present in only 50% of grade III and grade IV samples. Conversely, in some grade IV tumors that level of P16INK4 protein was elevated; in these cases, its target, CDK4, was amplified and overexpressed. These results suggest: (a) the involvement of P16INK4 in glioma progression; (b) that mechanisms other than mutation or deletion can down-regulate expression of the p16/CDKN2 gene; and (c) that the balance between CDK4 and its cognate inhibitor, P16INK4, may confer a cell growth advantage and facilitate tumor progression.
Nishikawa
R
R
Ludwig Institute for Cancer Research, University of California-San Diego, La Jolla 92093, USA.
Furnari
F B
FB
Lin
H
H
Arap
W
W
Berger
M S
MS
Cavenee
W K
WK
Su Huang
H J
HJ
D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018450:Disease Progression; D017353:Gene Deletion; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger