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<div> <div></div> <strong>Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer</strong></div> <p><strong>Nakarin Kitkumthorn,<sup>1,</sup><sup>2</sup> Pattamawadee Yanatatsanajit,<sup>1</sup> Sorapop Kiatpongsan,<sup>3</sup> Chureerat Phokaew,<sup>1</sup> Surang Triratanachat,<sup>3</sup> Prasert Trivijitsilp,<sup>3</sup> Wichai Termrungruanglert,<sup>3</sup> Damrong Tresukosol,<sup>3</sup> Somchai Niruthisard,<sup>3</sup> and Apiwat Mutirangura <sup>1,</sup><sup>4</sup></strong></p> <div><em><sup>1</sup>Molecular Biology and Genetics of Cancer Development Research Unit, Faculty of Medicine, Chulalongkorn University, Rama IV., Bangkok 10330, Thailand</em></div> <div><em><sup>2</sup>Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Rama IV., Bangkok 10330, Thailand</em></div> <div><em><sup>3</sup>Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Rama IV., Bangkok 10330, Thailand</em></div> <div><em><sup>4</sup>Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Rama IV., Bangkok 10330, Thailand</em></div> <div><span><em>Nakarin Kitkumthorn: </em><a href="mailto:Art_khuan@hotmail.com"><em>Art_khuan@hotmail.com</em></a><em>; </em></span><span><a></a><em>Pattamawadee Yanatatsanajit: </em><a href="mailto:Nuchjoe@hotmail.com"><em>Nuchjoe@hotmail.com</em></a><em>; </em></span><span><a></a><em>Sorapop Kiatpongsan: </em><a href="mailto:Ksorapop@yahoo.com"><em>Ksorapop@yahoo.com</em></a><em>; </em></span><span><a></a><em>Chureerat Phokaew: </em><a href="mailto:Hoshleys@hotmail.com"><em>Hoshleys@hotmail.com</em></a><em>; </em></span><span><a></a><em>Surang Triratanachat: </em><a href="mailto:Surangtrirattanachat@hotmail.com"><em>Surangtrirattanachat@hotmail.com</em></a><em>; </em></span><span><a></a><em>Prasert Trivijitsilp: </em><a href="mailto:Tprasert@chula.ac.th"><em>Tprasert@chula.ac.th</em></a><em>; </em></span><span><a></a><em>Wichai Termrungruanglert: </em><a href="mailto:Wichaiterm@hotmail.com"><em>Wichaiterm@hotmail.com</em></a><em>; </em></span><span><a></a><em>Damrong Tresukosol: </em><a href="mailto:Dtresukosol@hotmail.com"><em>Dtresukosol@hotmail.com</em></a><em>; </em></span><span><a></a><em>Somchai Niruthisard: </em><a href="mailto:Ndsomchai@hotmail.com"><em>Ndsomchai@hotmail.com</em></a><em>; </em></span><span><a></a><em>Apiwat Mutirangura: </em><a href="mailto:mapiwat@chula.ac.th"><em>mapiwat@chula.ac.th</em></a></span></div> <div> <div><a></a></div> <div>Background</div> <div>The aim of this study was to evaluate epigenetic status of <em>cyclin A1 </em>in human papillomavirus-associated cervical cancer. Y. Tokumaru <em>et al</em>., <em>Cancer Res </em><strong>64</strong>, 5982-7 (Sep 1, 2004)demonstrated in head and neck squamous-cell cancer an inverse correlation between <em>cyclin A1 </em>promoter hypermethylation and <em>TP53 </em>mutation. Human papillomavirus-associated cervical cancer, however, is deprived of TP53 function by a different mechanism. Therefore, it was of interest to investigate the epigenetic alterations during multistep cervical cancer development. </div> <div>Methods</div> <div>In this study, we performed duplex methylation-specific PCR and reverse transcriptase PCR on several cervical cancer cell lines and microdissected cervical cancers. Furthermore, the incidence of <em>cyclin A1 </em>methylation was studied in 43 samples of white blood cells, 25 normal cervices, and 24, 5 and 30 human papillomavirus-associated premalignant, microinvasive and invasive cervical lesions, respectively. </div> <div>Results</div> <div>We demonstrated <em>cyclin A1 </em>methylation to be commonly found in cervical cancer, both in vitro and in vivo, with its physiological role being to decrease gene expression. More important, this study demonstrated that not only is <em>cyclin A1 </em>promoter hypermethylation strikingly common in cervical cancer, but is also specific to the invasive phenotype in comparison with other histopathological stages during multistep carcinogenesis. None of the normal cells and low-grade squamous intraepithelial lesions exhibited methylation. In contrast, 36.6%, 60% and 93.3% of high-grade squamous intraepithelial lesions, microinvasive and invasive cancers, respectively, showed methylation. </div> <div>Conclusion</div> <div>This methylation study indicated that <em>cyclin A1 </em>is a potential tumor marker for early diagnosis of invasive cervical cancer.</div> <div> </div> <div> </div> </div> <div> <div> </div> <div> </div> <div></div> <div></div> <div></div> <div></div> <div></div> <div></div> <div><em>Source: BMC Cancer. 2006; 6: 55. </em></div> <div><em>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<span><a href="http://www.pubmedcentral.nih.gov/redirect3.cgi?&&reftype=extlink&artid=1435765&iid=125940&jid=16&&http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</a></span>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</em></div> </div>
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