This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Tokumaru, Y. Articles by Sidransky, D. Search for Related Content PubMed PubMed Citation Articles by Tokumaru, Y. Articles by Sidransky, D.

Inverse Correlation between Cyclin A1 Hypermethylation and p53 Mutation in Head and Neck Cancer Identified by Reversal of Epigenetic Silencing

¹ Department of Otolaryngology–Head and Neck Surgery, Head and Neck Cancer Research Division and ² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; and ³ Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea

Aberrant promoter hypermethylation of tumor suppressor genes is proposed to be a common feature of primary cancer cells. We recently developed a pharmacological unmasking microarray approach to screen unknown tumor suppressor gene candidates epigenetically silenced in human cancers. In this study, we applied this method to identify such genes in head and neck squamous cell carcinoma (HNSCC). We identified 12 novel methylated genes in HNSCC cell lines, including PGP9.5, cyclin A1, G0S2, bone-morphogenetic protein 2A, MT1G, and neuromedin U, which showed frequent promoter hypermethylation in primary HNSCC (60%, 45%, 35%, 25%, 25%, and 20%, respectively). Moreover, we discovered that cyclin A1 methylation was inversely related to p53 mutational status in primary tumors (P = 0.015), and forced expression of cyclin A1 resulted in robust induction of wild-type p53 in HNSCC cell lines. Pharmacological unmasking followed by microarray analysis is a powerful tool to identify key methylated tumor suppressor genes and relevant pathways.

This article has been cited by other articles:

				C. Welch, M. K. Santra, W. El-Assaad, X. Zhu, W. E. Huber, R. A. Keys, J. G. Teodoro, and M. R. Green Identification of a Protein, G0S2, That Lacks Bcl-2 Homology Domains and Interacts with and Antagonizes Bcl-2 Cancer Res., September 1, 2009; 69(17): 6782 - 6789. [Abstract] [Full Text] [PDF]

				K. L. Ostrow, H. L. Park, M. O. Hoque, M. S. Kim, J. Liu, P. Argani, W. Westra, W. V. Criekinge, and D. Sidransky Pharmacologic Unmasking of Epigenetically Silenced Genes in Breast Cancer Clin. Cancer Res., February 15, 2009; 15(4): 1184 - 1191. [Abstract] [Full Text] [PDF]

				M. Brait, S. Begum, A. L. Carvalho, S. Dasgupta, A. L. Vettore, B. Czerniak, O. L. Caballero, W. H. Westra, D. Sidransky, and M. O. Hoque Aberrant Promoter Methylation of Multiple Genes during Pathogenesis of Bladder Cancer Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2786 - 2794. [Abstract] [Full Text] [PDF]

				A. Restle, M. Farber, C. Baumann, M. Bohringer, K. H. Scheidtmann, C. Muller-Tidow, and L. Wiesmuller Dissecting the role of p53 phosphorylation in homologous recombination provides new clues for gain-of-function mutants Nucleic Acids Res., September 1, 2008; 36(16): 5362 - 5375. [Abstract] [Full Text] [PDF]

				M. O. Hoque, M. S. Kim, K. L. Ostrow, J. Liu, G. B. A. Wisman, H. L. Park, M. L. Poeta, C. Jeronimo, R. Henrique, A. Lendvai, et al. Genome-Wide Promoter Analysis Uncovers Portions of the Cancer Methylome Cancer Res., April 15, 2008; 68(8): 2661 - 2670. [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]

				K. Yamashita, M. S. Kim, H. L. Park, Y. Tokumaru, M. Osada, H. Inoue, M. Mori, and D. Sidransky HOP/OB1/NECC1 Promoter DNA Is Frequently Hypermethylated and Involved in Tumorigenic Ability in Esophageal Squamous Cell Carcinoma Mol. Cancer Res., January 1, 2008; 6(1): 31 - 41. [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]

				I. Ibanez de Caceres, E. Dulaimi, A. M. Hoffman, T. Al-Saleem, R. G. Uzzo, and P. Cairns Identification of novel target genes by an epigenetic reactivation screen of renal cancer. Cancer Res., May 15, 2006; 66(10): 5021 - 5028. [Abstract] [Full Text] [PDF]

				K. Yamashita, H. L. Park, M. S. Kim, M. Osada, Y. Tokumaru, H. Inoue, M. Mori, and D. Sidransky PGP9.5 Methylation in Diffuse-Type Gastric Cancer. Cancer Res., April 1, 2006; 66(7): 3921 - 3927. [Abstract] [Full Text] [PDF]

				S. Xi, K. F. Dyer, M. Kimak, Q. Zhang, W. E. Gooding, J. R. Chaillet, R. L. Chai, R. E. Ferrell, B. Zamboni, J. Hunt, et al. Decreased STAT1 Expression by Promoter Methylation in Squamous Cell Carcinogenesis J Natl Cancer Inst, February 1, 2006; 98(3): 181 - 189. [Abstract] [Full Text] [PDF]

				D. L. Mandelker, K. Yamashita, Y. Tokumaru, K. Mimori, D. L. Howard, Y. Tanaka, A. L. Carvalho, W.-W. Jiang, H. L. Park, M. S. Kim, et al. PGP9.5 Promoter Methylation Is an Independent Prognostic Factor for Esophageal Squamous Cell Carcinoma Cancer Res., June 1, 2005; 65(11): 4963 - 4968. [Abstract] [Full Text] [PDF]

				T. Mori, J. Kim, T. Yamano, H. Takeuchi, S. Huang, N. Umetani, K. Koyanagi, and D. S.B. Hoon Epigenetic Up-regulation of C-C Chemokine Receptor 7 and C-X-C Chemokine Receptor 4 Expression in Melanoma Cells Cancer Res., March 1, 2005; 65(5): 1800 - 1807. [Abstract] [Full Text] [PDF]