Lack of germ-line mutations of CDK4, p16(INK4A), and p15(INK4B) in families with glioma.
Gliomas are tumors of the central nervous system that may be inherited in some patients. The gene(s) responsible for the clustering of gliomas in families have not yet been identified. Molecular studies of sporadic high-grade gliomas have revealed mutations or deletions of the genes encoding the protein kinase inhibitors p16(INK4A) and p15(INK4B) in a large proportion of tumors. Moreover, those tumors without deletions frequently display gene amplification and/or over-expression of mRNA encoding the protein kinase cdk4. We hypothesized that germ-line mutations in the p16(INK4A), p15(INK4B), or CDK4 genes might contribute to some cases of familial gliomas. To address this issue, we analyzed 36 kindreds with a predisposition to glial tumors. Genomic DNA from index members of these families was screened by PCR-single-strand conformational polymorphism analysis. We did not detect any functional mutations in the p16(INK4A), p15(INK4B), or CDK4 genes, although two individuals did have a previously described A140T polymorphism in p16(INK4A). Thus, despite the association between the sporadic forms of high-grade glioma and abnormalities of p16(INK4A), p15(INK4B), or CDK4, we found no evidence that germ-line mutations in the coding region of these three genes predispose to inherited glial tumors.
Gao
L
L
Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Liu
L
L
van Meyel
D
D
Cairncross
G
G
Forsyth
P
P
Kimmel
D
D
Jenkins
R B
RB
Lassam
N J
NJ
Hogg
D
D
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D016000:Cluster Analysis; D051358:Cyclin-Dependent Kinase 4; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D005190:Family; D005260:Female; D005784:Gene Amplification; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D005910:Glioma / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases