Unit:
Τομέας ΚλινικοεργαστηριακόςLibrary of the School of Health Sciences
Dissertation committee:
Ιωάννης Γ. Παναγιωτίδης, Αν. Καθηγητής, Ιατρικής, ΕΚΠΑ
Πέτρος Καρακίτσος, Καθηγητής, Ιατρικής, ΕΚΠΑ
Περικλής Φούκας, Επ.Καθηγητής, Ιατρικής, ΕΚΠΑ
Νικόλαος Παπαντωνίου, Καθηγητής, Ιατρικής, ΕΚΠΑ
Νικόλαος Καβαντζάς, Καθηγητής, Ιατρικής, ΕΚΠΑ
Χαράλαμπος Χρέλιας, Αν. Καθηγητής, Ιατρικής, ΕΚΠΑ
Σωτήριος Τσιόδρας, Αν. Καθηγητής, Ιατρικής, ΕΚΠΑ
Original Title:
Συμβολή της μεθυλίωσης ως επιγενετικό φαινόμενο στην ανάπτυξη προκαρκινωματωδών αλλοιώσεων του τραχήλου της μήτρας
Summary:
OBJECTIVE: Cervical cancer based on World Health Organization data, is second in frequency among women between the ages of 15-44 years and the third for all ages. In the development of cervical cancer necessary event considered the transfection by a high risk type of the human papillomavirus (HPV), but additive effect appear to have and other epigenetic phenomenon such as gene silencing, which include DNA methylation in the promoter of tumor suppressor genes.
The aim of this study was to investigate the clinical significance of methylation detecting the methylation in eight promoter tumor suppressor genes and the importance of methylation of promoter in women default clinically healthy with an increased risk of cervical cancer of the uterus, and the correlation of epigenetic event with severity of intraepithelial lesion and the possibility of evolution.
MATERIALS AND METHODS: All examinations were performed on the basis of project “AKAKOS” and project "HPVGuard
765 histologically confirmed cases and 959 liquid based cytology samples were used for detection of HPV DNA. For the methylation of the promoters of tumor suppressor genes was performed conversion of unmethylated cytosines to uracil after treatment with bisulfite. The methylation of CDKN2A, MGMT, hMLH-1 and SPARC was identified with methylation specific PCR (MSP) and their products analyzed in 2% agarose gel. The methylation of MAL-1, CADM-1, RARβ and DAPK1 performed by Real-time PCR using specific primers and Taqman probes (MethyLight), which separate the methylated from unmethylated form.
RESULTS: Positivity for HPV DNA is statistically significant increase with increasing severity of the lesion both categories CIN2+ and CIN3+, with correlation of HPV 16, 31, 33, 52. In CIN2+ methylation has correlation with detection of 14HR (AUC 0.712), while in CIN3+ is correlated with detection of HPV16 (AUC 0.721). From the 8th analyzed genes best results showed the percentage of genes that were methylation followed by methylation of MAL-1 and SPARC for CIN2+ (AUC 0.654), for CIN3+ (AUC 0.706) and cancers (AUC 0.957).
CONCLUSIONS: Methylation recognized important for CIN2+ and more important for CIN3+ and cancers. It is rare event in in pre-cancerous lesions and in younger women showing lower positivity and correlated with specific types of HPV.
Main subject category:
Health Sciences
Keywords:
Cervical cancer, Methylation, HPV, Tumor suppressor genes
Number of references:
332
File:
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Aga Evangelia PhD.pdf
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