title: Expression and methylation pattern of p16 in neuroblastoma tumorigenesis.
abstract: Understanding migration, population and differentiation of primordial neural crest cells will help in evolving biology of neuroblastoma. P16 is a tumour suppressor gene contributing in cell cycle arrest as cyclin dependent kinase inhibitor. Methylation is an important mechanism for silencing tumor suppressor genes. The aim of this study was to evaluate the role of p16 and its methylation pattern in neuroblastoma tumorigenesis. This study included 23 cases (11 male; 12 female) and 31 samples from archival paraffin embedded tissues. P16 was studied in 5 samples of normal adrenal medullar tissue, 5 samples of adrenal tissue including blastic rests, 5 samples of neuroblastoma in situ tissue and in 8 samples of neuroblastoma tissues primary and after chemotherapy in each group. The adrenal gland tissues were obtained from paediatric autopsy cases. Expression of p16 was searched by immunohistochemistry. Methylation specific PCR was used to detect the methylation rate of p16. The age range of autopsy cases was between 20 weeks of foetal age and 36 months of infant age. The mean age of neuroblastoma cases was 45 months. P16 expression was positive in normal adrenal tissues, in one of 5 samples of adrenal blastic rest tissue and in all of samples of after chemotherapy; while no expression was observed in neuroblastoma and neuroblastoma in situ tissues. P16 methylation was observed in samples of neuroblastoma in situ and primary neuroblastoma tissues. Our results suggest that p16 and its methylation seems to play role in neuroblastoma tumorigenesis and in the migration, population and differentiation of primordial neural crest cells. Inhibitors of DNA methylation may provide a useful tool for restoring p16 activity in neuroblastoma treatment.
authors.affiliation: Institute of Oncology, Dokuz Eylul University, Izmir, Turkey. safiyeaktas@yahoo.com
authors.forename: Safiye
authors.initials: S
authors.lastname: Aktas
authors.forename: Aydan Cavusoglu
authors.initials: AC
authors.lastname: Celebiler
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Zadeoğlulari
authors.forename: Gulden
authors.initials: G
authors.lastname: Diniz
authors.forename: Aydanur
authors.initials: A
authors.lastname: Kargi
authors.forename: Nur
authors.initials: N
authors.lastname: Olgun
mesh_terms: D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D005333:Fetus; D015870:Gene Expression; D019942:Genes, p16; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D016133:Polymerase Chain Reaction