NDLI: Sequential gene promoter methylation during HPV-induced cervical carcinogenesis

Content Provider	PubMed Central
Author	Henken, F. E. Wilting, S. M. Overmeer, R. M. Nygren, A. O. H. Errami, A. Schouten, J. P. Meijer, C. J. L. M. Snijders, P. J. F. Steenbergen, R. D. M. Van Rietschoten, J. G. I.
Copyright Year	2007
Abstract	We aimed to link DNA methylation events occurring in cervical carcinomas to distinct stages of HPV-induced transformation. Methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) analysis of cervical carcinomas revealed promoter methylation of 12 out of 29 tumour suppressor genes analysed, with MGMT being most frequently methylated (92%). Subsequently, consecutive stages of HPV16/18-transfected keratinocytes (n=11), ranging from pre-immortal to anchorage-independent phenotypes, were analysed by MS-MLPA. Whereas no methylation was evident in pre-immortal cells, progression to anchorage independence was associated with an accumulation of frequent methylation events involving five genes, all of which were also methylated in cervical carcinomas. TP73 and ESR1 methylation became manifest in early immortal cells followed by RARβ and DAPK1 methylation in late immortal passages. Complementary methylation of MGMT was related to anchorage independence. Analysis of nine cervical cancer cell lines, representing the tumorigenic phenotype, revealed in addition to these five genes frequent methylation of CADM1, CDH13 and CHFR. In conclusion, eight recurrent methylation events in cervical carcinomas could be assigned to different stages of HPV-induced transformation. Hence, our in vitro model system provides a valuable tool to further functionally address the epigenetic alterations that are common in cervical carcinomas.
Related Links	http://dx.doi.org/10.1038/sj.bjc.6604055
Ending Page	1464
Page Count	8
Starting Page	1457
File Format	PDF
ISSN	00070920
e-ISSN	15321827
Journal	British Journal of Cancer
Issue Number	10
Volume Number	97
Language	English
Publisher	Nature Publishing Group
Publisher Date	2007-11-19
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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