This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maruya, S.-i. Articles by El-Naggar, A. K. Search for Related Content PubMed PubMed Citation Articles by Maruya, S.-i. Articles by El-Naggar, A. K.

Differential Methylation Status of Tumor-Associated Genes in Head and Neck Squamous Carcinoma

Incidence and Potential Implications

Departments of ¹ Pathology, ² Leukemia, ³ Head and Neck Surgery, ⁴ Radiation Oncology, and ⁵ Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Purpose: Promoter hypermethylation is one of the major mechanisms in the transcriptional inactivation of certain carcinoma-associated genes. Concurrent methylation analysis of multiple, functionally distinct genes may provide important information on their differential alterations and potential association in head and neck squamous carcinogenesis.

Experimental Design: Methylation-specific PCR analysis of the CpG islands of 8 cancer-related genes was performed on 19 cell lines and 32 primary head and neck squamous cell carcinoma (HNSC) specimens with matched histologically normal mucosa and 6 dysplastic lesions. The methylation status and histological features of the specimens were investigated.

Results: In histologically normal squamous mucosa, no to low-level methylation (0–22%) was noted in some specimens at all genes except RARß2 (50%). Considerable variation in the incidence of methylation of these genes within and between cell lines and tumor specimens was noted. The highest incidences of methylation in the cell lines and primary tumors were noted in RARß2 (53%), MGMT (37%), p16 (33%), and DAP-K (25%); low incidence of methylations were noted in E-cadherin (2%), p73 (2%) RASSF1A (10%), and p14 (20%) genes. The incidences of methylation of each gene were almost similar between the HNSC cell lines and primary cancer specimens, although methylation of RASSF1A was observed in cell line (26%), but not in dysplasia and primary tumor. RARß, p16, and MGMT genes showed the highest incidences of methylation in premalignant and invasive carcinomas.

Conclusions: Methylation of p16, RARß, and MGMT may constitute early events in HNSC tumorigenesis. The infrequent methylation at certain genes suggests a minimal role for this feature in their functional assessment in HNSC. The variability within and between cell lines and tumor specimens supports a heterogeneous and dynamic state of methylation in genes associated with HNSC tumorigenesis.

This article has been cited by other articles:

				K.-H. Huang, S.-F. Huang, I-H. Chen, C.-T. Liao, H.-M. Wang, and L.-L. Hsieh Methylation of RASSF1A, RASSF2A, and HIN-1 Is Associated with Poor Outcome after Radiotherapy, but not Surgery, in Oral Squamous Cell Carcinoma Clin. Cancer Res., June 15, 2009; 15(12): 4174 - 4180. [Abstract] [Full Text] [PDF]

				S.P. Barros and S. Offenbacher Epigenetics: Connecting Environment and Genotype to Phenotype and Disease Journal of Dental Research, May 1, 2009; 88(5): 400 - 408. [Abstract] [Full Text] [PDF]

				K. C. A. Chan, P. B. S. Lai, T. S. K. Mok, H. L. Y. Chan, C. Ding, S. W. Yeung, and Y. M. D. Lo Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma Clin. Chem., September 1, 2008; 54(9): 1528 - 1536. [Abstract] [Full Text] [PDF]

				E.-S. Lee, J.-P. Issa, D. B. Roberts, M. D. Williams, R. S. Weber, M. S. Kies, and A. K. El-Naggar Quantitative Promoter Hypermethylation Analysis of Cancer-Related Genes in Salivary Gland Carcinomas: Comparison with Methylation-Specific PCR Technique and Clinical Significance Clin. Cancer Res., May 1, 2008; 14(9): 2664 - 2672. [Abstract] [Full Text] [PDF]

				R. J. Shaw, G. L. Hall, D. Lowe, T. Liloglou, J. K. Field, P. Sloan, and J. M. Risk The Role of Pyrosequencing in Head and Neck Cancer Epigenetics: Correlation of Quantitative Methylation Data With Gene Expression Arch Otolaryngol Head Neck Surg, March 1, 2008; 134(3): 251 - 256. [Abstract] [Full Text] [PDF]

				A. L. Carvalho, C. Jeronimo, M. M. Kim, R. Henrique, Z. Zhang, M. O. Hoque, S. Chang, M. Brait, C. S. Nayak, W.-W. Jiang, et al. Evaluation of Promoter Hypermethylation Detection in Body Fluids as a Screening/Diagnosis Tool for Head and Neck Squamous Cell Carcinoma Clin. Cancer Res., January 1, 2008; 14(1): 97 - 107. [Abstract] [Full Text] [PDF]

				K. Chen, R. Sawhney, M. Khan, M. S. Benninger, Z. Hou, S. Sethi, J. K. Stephen, and M. J. Worsham Methylation of Multiple Genes as Diagnostic and Therapeutic Markers in Primary Head and Neck Squamous Cell Carcinoma Arch Otolaryngol Head Neck Surg, November 1, 2007; 133(11): 1131 - 1138. [Abstract] [Full Text] [PDF]

				T. Martone, A. Gillio-Tos, L. De Marco, V. Fiano, M. Maule, A. Cavalot, M. Garzaro, F. Merletti, and G. Cortesina Association Between Hypermethylated Tumor and Paired Surgical Margins in Head and Neck Squamous Cell Carcinomas Clin. Cancer Res., September 1, 2007; 13(17): 5089 - 5094. [Abstract] [Full Text] [PDF]

				M. D. Williams, N. Chakravarti, M. S. Kies, S.-I. Maruya, J. N. Myers, J. C. Haviland, R. S. Weber, R. Lotan, and A. K. El-Naggar Implications of Methylation Patterns of Cancer Genes in Salivary Gland Tumors Clin. Cancer Res., December 15, 2006; 12(24): 7353 - 7358. [Abstract] [Full Text] [PDF]

				M. J. Worsham, K. M. Chen, V. Meduri, A. O. H. Nygren, A. Errami, J. P. Schouten, and M. S. Benninger Epigenetic events of disease progression in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg, June 1, 2006; 132(6): 668 - 677. [Abstract] [Full Text] [PDF]

				B Perez-Ordonez, M Beauchemin, and R C K Jordan Molecular biology of squamous cell carcinoma of the head and neck. J. Clin. Pathol., May 1, 2006; 59(5): 445 - 453. [Abstract] [Full Text] [PDF]