title: High expression of DNA methyltransferases in primary human medulloblastoma.
abstract: Epigenetic alterations have been implicated in cancer development. DNA methylation modulates gene expression, which is catalyzed by DNA methyltransferases (DNMTs). The objective of our study was to evaluate expression of DNMTs in medulloblastoma and analyze its correlation with clinical features. Nuclear expression of DNMT1, DNMT3A and DNMT3B was analyzed in human primary medulloblastoma of 44 patients using immunohistochemistry. Correlation of expression of DNMT levels with classical histological subtypes, novel molecular subgroups and survival of patients was analyzed. Elevated expression of DNMT1, DNMT3A and DNMT3B was observed in 63.64%, 68.18% and 72.73% of all cases, respectively. None of them showed a correlation with classical histology or survival. Concerning molecular subtypes, significantly higher expression of DNMT1 was observed in the SHH group compared to non-SHH samples (p = 0.02), but without significant difference in DNMT3A or DNMT3B levels between any subtypes. In conclusion, DNMT1, DNMT3A and DNMT3B are highly expressed in human medulloblastoma samples, suggesting that promoter hypermethylation may play a role in medulloblastoma development. Demethylation of tumor suppressor gene promoters may be considered as a possible future target in therapy of medulloblastoma.
authors.forename: T
authors.initials: T
authors.lastname: Pócza
authors.forename: T
authors.initials: T
authors.lastname: Krenács
authors.forename: E
authors.initials: E
authors.lastname: Turányi
authors.forename: J
authors.initials: J
authors.lastname: Csáthy
authors.forename: Z
authors.initials: Z
authors.lastname: Jakab
authors.affiliation: Peter Hauser, 2nd Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, H-1094 Budapest, Hungary, phone: +36(1)2151380, fax: +36(1)2151381, e-mail: hauserpeti@yahoo.com.
authors.forename: P
authors.initials: P
authors.lastname: Hauser
mesh_terms: D000293:Adolescent; D000328:Adult; D002528:Cerebellar Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D019175:DNA Methylation / Q000502:physiology; D000090205:DNA Methyltransferase 3A; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human