Abstract
Lung cancer is recognized as a leading cause of cancer-related death worldwide and its frequency is still increasing. The prognosis in lung cancer is poor and limited by the difficulties of diagnosis at early stage of disease, when it is amenable to surgery treatment. Therefore, the advance in identification of lung cancer genetic and epigenetic markers with diagnostic and/or prognostic values becomes an important tool for future molecular oncology and personalized therapy. As in case of other tumors, aberrant epigenetic landscape has been documented also in lung cancer, both at early and late stage of carcinogenesis. Hypermethylation of specific genes, mainly tumor suppressor genes, as well as hypomethylation of oncogenes and retrotransposons, associated with histopathological subtypes of lung cancer, has been found. Epigenetic aberrations of histone proteins and, especially, the lower global levels of histone modifications have been associated with poorer clinical outcome in lung cancer. The recently discovered role of epigenetic modifications of microRNA expression in tumors has been also proven in lung carcinogenesis. The identified epigenetic events in lung cancer contribute to its specific epigenotype and correlated phenotypic features. So far, some of them have been suggested to be cancer biomarkers for early detection, disease monitoring, prognosis, and risk assessment. As epigenetic aberrations are reversible, their correction has emerged as a promising therapeutic target.
Highlights
Nowadays it is clearly acknowledged, that during neoplastic transformation genetic lesions are accompanied by important epigenetic modifications
The study results have shown that treatment with histone deacetylases (HDACs) inhibitor via increasing histone acetylation results in increased expression of many genes encoding suppressors of invasion and metastasis, negative cell-cycle regulators and apoptosis-related proteins [65]
The results revealed that tumor Long interspersed element (LINE)-1 methylation status may help to select early-stage Non-Small Cell Lung Carcinoma (NSCLC) patients requiring adjuvant treatment after curative surgery [98]
Summary
Nowadays it is clearly acknowledged, that during neoplastic transformation genetic lesions are accompanied by important epigenetic modifications. Epigenetic mechanisms, related to inherited changes in gene expression without alterations in the primary DNA sequence [8, 9], are essential for normal cellular functioning. They play important role in genome activity regulations, encompassing key biological processes, such as differentiation and embryonic development, tissue-specific gene expression regulation or imprinting and X chromosome silencing in females. The final result of epigenetic modifications, listed, is the altered structure of chromatin involved in packaging of the human genome This process, the so called chromatin remodeling, is associated with chromatin conformational changes into functionally active structure (euchromatin) or inactive condensed form (heterochromatin) [1, 11, 12].
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