Page 15 - ABSTRAKTI SDIR3

the DNA methylation of cytosine located 5’‘to guanosine in a CpG dinucleotide. Cy-
tosine methylation of “CpG islands” in the promoters of tumor suppressor genes
causes their inactivation, transcriptional silencing and malignant transformation.
Posttranslational modifications of histones are important in transcriptional regu-
lation. Newer investigations revealed an emerging role of non-coding RNAs in epi-
genetic regulation of gene expression in translational inhibition or degradation of
the mRNA. Since epigenetic changes are early event in malignant transformation,
perspectives of epigenetic researches in molecular medicine are focused toward
early and non-invasive cancer diagnostics, prognosis, prediction and introduction
of epigenetic therapy.

Diagnostic significance of epigenetic changes

The development of PCR method for the detection of methylated DNA, methyl-
ation of 1 of 50 000 allele can be detected, both in the tumors as well as in body
fluids. This provided a wide range of possibilities for the use of DNA methyla-
tion in the early detection and diagnosis of cancers. In the sputum of smokers
pre-cancerous changes can be detected on the basis of hypermethylation of p16
and MGMT genes, up to three years prior to clinical manifestation of lung cancer.
Development of REAL-TIME technology showed that measuring quantification of
the methylation of glutathione synthetase GST1 gene in prostate tumors it is pos-
sible to differentiate benign from malignant changes.

Prognostic significance of epigenetic changes

LECTURES Promoter hypermethylation of DAPK gene is associated with aggressiveness and
poor prognosis in lung cancer. Hypermethylation of the gene promoter for the
E-cadherin is a predictor of poor outcome of diffuse gastric carcinoma, non-small
cell lung cancer, and oral squamous cell carcinoma. Hypermethylation of p16 is
correlated with poor prognosis in head and neck cancers.
SDIR - 3 Predictive significance of epigenetic changes

Hypermethylation MGMT gene is a prognostic factor for a good response to al-
kylating chemotherapy in glioma and oral squamous cell carcinoma, as well as in
the therapy of cyclophosphamide in diffuse large B-cell lymphoma Promoter hy-
3 permethylation WRN gene is associated with a hypersensitivity to the topoisom-
erase inhibitor irinotecan in primary colon carcinoma. Hypermethylation of DNA