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 Wong, T. S. Articles by Yuen, A. P.-W. Search for Related Content PubMed PubMed Citation Articles by Wong, T. S. Articles by Yuen, A. P.-W.

Promoter Hypermethylation of High-in-normal 1 Gene in Primary Nasopharyngeal Carcinoma¹

Departments of Surgery [T. S. W., W. I. W., A. P-W. W.], Clinical Oncology [D. L-W. K., J. S-T. S.], Medicine [Y. L. K.], and Anatomy [S. W. T.], The University of Hong Kong, Hong Kong, SAR China

Purpose: The methylation of high-in-normal-1 (HIN-1) gene promoter in undifferentiated nasopharyngeal carcinoma (NPC) is studied.

Experimental design: The methylation status of HIN-1 in NPC cell lines, primary NPC, paired nasopharyngeal swabs, paired throat-rinsing fluid, and paired peripheral blood was assessed by methylation-specific PCR assay. The relationship between HIN-1 promoter methylation and transcription in NPC cell lines was evaluated by reverse transcription-PCR and demethylation agent treatment (5-aza-2-deoxycytidine).

Results: Hypermethylated promoter was observed in five of five (100%) NPC cell lines and not found in three normal nasopharyngeal outgrowths, two tonsil epithelial cell cultures, and two skin fibroblast cultures. Reverse transcription-PCR assay indicated that HIN-1 transcription was significantly down-regulated in the NPC cell line with promoter methylation. Treatment with demethylation agent, 5-aza-2-deoxycytidine, restored HIN-1 transcription in the NPC cell line. Methylated HIN-1 promoter was found in 36 of 47 (77%) primary NPC tumors and not found in the normal nasopharyngeal biopsies. Methylated HIN-1 promoter was detected in 12 of 26 (46%) nasopharyngeal swabs, 5 of 26 (19%) throat-rinsing fluids, 2 of 11 (18%) plasmas, and 5 of 11 (46%) buffy coats of peripheral blood of the NPC patients but was not detectable in all normal controls.

Conclusion: HIN-1 promoter hypermethylation is common in NPC. Methylated promoter DNA in nasopharyngeal swab, throat-rinsing fluid, and peripheral blood might be potentially useful as tumor marker for screening of NPC.

This article has been cited by other articles:

				Q. Yang, C. M. Kiernan, Y. Tian, H. R. Salwen, A. Chlenski, B. A. Brumback, W. B. London, and S. L. Cohn Methylation of CASP8, DCR2, and HIN-1 in Neuroblastoma Is Associated with Poor Outcome Clin. Cancer Res., June 1, 2007; 13(11): 3191 - 3197. [Abstract] [Full Text] [PDF]

				I. Krop, M. T. Parker, N. Bloushtain-Qimron, D. Porter, R. Gelman, H. Sasaki, M. Maurer, M. B. Terry, R. Parsons, and K. Polyak HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation Cancer Res., November 1, 2005; 65(21): 9659 - 9669. [Abstract] [Full Text] [PDF]

				I. Krop, A. Player, A. Tablante, M. Taylor-Parker, J. Lahti-Domenici, J. Fukuoka, S. K. Batra, N. Papadopoulos, W. G. Richards, D. J. Sugarbaker, et al. Frequent HIN-1 Promoter Methylation and Lack of Expression in Multiple Human Tumor Types Mol. Cancer Res., September 1, 2004; 2(9): 489 - 494. [Abstract] [Full Text] [PDF]