title: Epigenetic and genetic alterations affect the WWOX gene in head and neck squamous cell carcinoma.
abstract: Different types of genetic and epigenetic changes are associated with HNSCC. The molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive investigation. WWOX gene expression is altered in many cancers and in a recent work reduced WWOX expression has been associated with miR-134 expression in HNSCC. In this study we investigated the WWOX messenger RNA expression levels in association with the promoter methylation of the WWOX gene and miR-134 expression levels in 80 HNSCC tumor and non-cancerous tissue samples. Our results show that WWOX expression is down-regulated especially in advanced-stage tumor samples or in tumors with SCC. This down-regulation was associated with methylation of the WWOX promoter region but not with miR-134 expression. There was an inverse correlation between the expression level and promoter methylation. We also analyzed whole exons and exon/intron boundries of the WWOX gene by direct sequencing. In our study group we observed 10 different alterations in the coding sequences and 18 different alterations in the non-coding sequences of the WWOX gene in HNSCC tumor samples. These results indicate that the WWOX gene can be functionally inactivated by promoter methylation, epigenetically or by mutations affecting the sequences coding for the enzymatic domain of the gene, functionally. We conclude that inactivation of WWOX gene contributes to the progression of HNSCC.
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Biology, Istanbul, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Ekizoglu
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Biology, Istanbul, Turkey.
authors.forename: Pelin
authors.initials: P
authors.lastname: Bulut
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology, Istanbul, Turkey.
authors.forename: Emin
authors.initials: E
authors.lastname: Karaman
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology, Istanbul, Turkey.
authors.forename: Erkan
authors.initials: E
authors.lastname: Kilic
authors.affiliation: Istanbul University, Cerrahpasa Medical Faculty, Department of Medical Biology, Istanbul, Turkey.
authors.forename: Nur
authors.initials: N
authors.lastname: Buyru
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human