Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation
Corresponding Author
Daniel Weiss
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Muenster, Kardinal-von-Galen Ring 10, 48149 Muenster, Germany.Search for more papers by this authorTuerker Basel
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Search for more papers by this authorFlorian Sachse
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Search for more papers by this authorAndreas Braeuninger
Department of Molecular Pathology, University of Muenster, Muenster, Germany
Search for more papers by this authorClaudia Rudack
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Search for more papers by this authorCorresponding Author
Daniel Weiss
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Muenster, Kardinal-von-Galen Ring 10, 48149 Muenster, Germany.Search for more papers by this authorTuerker Basel
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Search for more papers by this authorFlorian Sachse
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Search for more papers by this authorAndreas Braeuninger
Department of Molecular Pathology, University of Muenster, Muenster, Germany
Search for more papers by this authorClaudia Rudack
Department of Otorhinolaryngology, Head and Neck Surgery, University of Muenster, Muenster, Germany
Search for more papers by this authorAbstract
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. © 2011 Wiley-Liss, Inc.
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