title: Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation.
abstract: Aberrant promoter methylation of specific genes and infection with human papillomavirus 16 (HPV16) are known risk factors for the development of Head and Neck Squamous Cell Carcinoma (HNSCC). Little knowledge exists on the interaction of HPV16 infection and promoter methylation in HNSCC. The promoter methylation status of 12 genes (TIMP3, CDH1, CDKN2A, DAPK1, transcription factor 21 (TCF21), CD44, MLH1, MGMT, RASSF1, cyclin A1 (CCNA1), LARS2, and CEBPA) was evaluated by methylation-specific polymerase chain reaction in 55 primary HNSCC and 31 controls. The results were correlated with HPV16 status and clinicopathological characteristics. CCNA1 and p53 protein expression were additionally determined by immunohistochemistry and compared with p53 mutation status. Methylation of DAPK1 (P = 0.043), CCNA1 (P = 0.016) and TCF21 (P = 0.0005) was significantly more present in HNSCC than in controls. The genes TIMP3 (P = 0.018) and CCNA1 (P = 0.015) showed higher methylation frequency in HPV16 positive HNSCC compared to HPV16 negative tumors. CCNA1 methylation did not correlate with CCNA1 protein expression and p53 mutation, respectively. Methylation of TCF21 was associated with higher age (P = 0.044) and nicotine abuse (P = 0.035). Methylation of CCNA1 was significantly more present in females (P = 0.003). Methylation of TCF21 and CCNA1 are important risk factors for HNSCC development. CCNA1 methylation may play a crucial role in HPV16-induced carcinogenesis of HNSCC independently of p53.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weiss
authors.forename: Tuerker
authors.initials: T
authors.lastname: Basel
authors.forename: Florian
authors.initials: F
authors.lastname: Sachse
authors.forename: Andreas
authors.initials: A
authors.lastname: Braeuninger
authors.forename: Claudia
authors.initials: C
authors.lastname: Rudack
mesh_terms: D000368:Aged; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000821:virology*; D056750:Cyclin A1 / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000821:virology*; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
chemical_list: D056750:Cyclin A1; D017931:DNA Primers