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Aberrant DNA methylation in HPV associated lesions

Principal investigator

Category
Znanstveni projekti Ministarstva znanosti, obrazovanja i športa
Project code
098-0982464-2510
Start date
Feb 1st 2007
End date
Dec 31st 2011
Status
Done

Cervical cancer is an important cause of death from cancer in women worldwide. The process of cervical oncogenesis takes a very long period of time and happens in only a few women infected with human papillomavirus (HPV) with high oncogenic potential. Persistent infection is necessary for development of cervical cancer. The integration of viral genome into host cell genome is the essential event for maintenance of the persistent infection, where the continuous expression of viral oncogenes E6 and E7 is assured. Inactivation of the tumour suppressor p53 and Rb by the E6 and E7 proteins, respectively, is an important process in maintaining abnormal cellular proliferation by inactivating normal cell cycle checkpoints. In addition, to HPV infection, it is clear that other factors are also involved in cervical carcinogenesis. In the development of cancer, tumour suppressor genes are inactivated by a number of processes including point mutation and chromosomal deletion, but also by epigenetic silencing of tumour suppressor genes by promoter hypermethylation that is also commonly seen in human cancer. Recently, in several studies, an aberrant methylation pattern was found during the multistage pathogenesis of cervical cancer with a trend of increasing methylation with increasing pathological changes. In the present study, we intend to examine aberrant methylation of CpG islands within the promoter regions of a panel of genes that are frequently methylated in cervical cancer or other malignancies and are involved in cell cycle control, DNA mismatch repair, adhesion, apoptosis, differentiation and metastasis. The aberrant methylation status will also be evaluated in the HPV genome beside the type and the physical state of the virus. These epigenetic changes will be evaluated in cervical scrapes of women with abnormal cytology and cervical cancer patients in order to find the best candidate(s) for prognostic factors of cervical cancer development and invasion.

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