Analysis of cell cycle regulators: p16INK4A, pRb, and CDK4 in low- and high-grade meningiomas.
Abnormalities in the p16INK4A, CDK4, and Rb genes, which regulate transition through G1 phase of the cell cycle, have been implicated in the progression of diverse types of cancer. To evaluate the involvement of p16INK4A, CDK4, and Rb in the tumorigenesis of meningiomas, the status of these genes or gene products were examined. The genetic alteration of the p16INK4A gene was examined by homozygous deletions and by mutation analysis. The methylation status of the p16INK4A was determined by Southern blotting. Neither homozygous deletions nor point mutations of the p16INK4A gene were observed in any of the 23 meningiomas. Partial rather than complete methylation of the p16INK4A gene at SacII or SmaI sites was shown in five (23.8%) meningiomas. The methylation status of the p16INK4A gene was not consistently associated with the expression of p16INK4A in meningiomas. These results suggest that the true relationship between methylation and expression of p16INK4A may be obscured in a complex manner by various mechanisms that regulate p16INK4A expression. Aberrant expressions of pRb and CDK4 were not observed in any of the meningiomas we examined, indicating that abnormalities of the pRb and CDK4 appear to be rare in meningiomas.
Tse
J Y
JY
Department of Anatomical & Cellular Pathology, The Chinese University of Hong Kong.
Ng
H K
HK
Lo
K W
KW
Chong
E Y
EY
Lam
P Y
PY
Ng
E K
EK
Poon
W S
WS
Huang
D P
DP
D000293:Adolescent; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018900:Dinucleotide Repeats; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016161:Genes, Retinoblastoma / Q000235:genetics; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D019656:Loss of Heterozygosity; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000235:genetics
D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases