CDKN2A, CDKN2B and p14ARF are frequently and differentially methylated in ependymal tumours.
Ependymal tumours are histologically and clinically varied lesions. Numerical abnormalities of chromosome 9 are frequently associated with these tumours. Nevertheless, the three important tumour suppressor genes located in this chromosome, CDKN2A, CDKN2B and p14 ARF, have not been reported to be commonly altered in them. We studied promoter methylation of these genes, an important mechanism associated with gene silencing in a series of 152 ependymal tumours of WHO grades I to III. Methylation status of the CDKN2A, CDKN2B and p14 ARF promoters was assessed by methylation-specific polymerase chain reaction and the genetic results were correlated to clinicopathological features. We observed promoter methylation for CDKN2A in 21% (26/123) of tumours, for CDKN2B in 32% (23/71) and p14 ARF in 21% (23/108). For all three genes, posterior fossa ependymomas were less frequently methylated in paediatric patients than in adults. For CDKN2B, extracranial tumours were more frequently methylated than intracranial ones. For CDKN2B and p14 ARF, methylation was more frequent in low-grade tumours; the reverse was observed for CDKN2A. CDKN2A, CDKN2B and p14 ARF promoters were methylated in 21-32% of the tumours. Frequencies of methylation varied according to clinicopathological features. This suggests a role for these genes in ependymoma tumorigenesis.
Rousseau
E
E
Laboratory of Neuropathology, Université Catholique de Louvain, Brussels, Belgium.
Ruchoux
M-M
MM
Scaravilli
F
F
Chapon
F
F
Vinchon
M
M
De Smet
C
C
Godfraind
C
C
Vikkula
M
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004806:Ependymoma / Q000235:genetics*; D019942:Genes, p16; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D013120:Spinal Cord Neoplasms / Q000235:genetics; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D025521:Tumor Suppressor Proteins