1. Promoter Methylation of Selected Genes in Non-Small-Cell Lung Cancer Patients and Cell Lines.
- Author
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Sarne V, Huter S, Braunmueller S, Rakob L, Jacobi N, Kitzwögerer M, Wiesner C, Obrist P, and Seeboeck R
- Subjects
- Aged, Antigens, CD metabolism, Biomarkers, Tumor metabolism, Cadherins metabolism, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung metabolism, Female, Humans, Lung Neoplasms genetics, Lung Neoplasms metabolism, Male, Middle Aged, Prognosis, Tumor Cells, Cultured, Antigens, CD genetics, Biomarkers, Tumor genetics, Cadherins genetics, Carcinoma, Non-Small-Cell Lung pathology, DNA Methylation, Gene Expression Regulation, Neoplastic, Lung Neoplasms pathology, Promoter Regions, Genetic
- Abstract
Specific gene promoter DNA methylation is becoming a powerful epigenetic biomarker in cancer diagnostics. Five genes ( CDH1 , CDKN2Ap16 , RASSF1 A , TERT , and WT1 ) were selected based on their frequently published potential as epigenetic markers. Diagnostic promoter methylation assays were generated based on bisulfite-converted DNA pyrosequencing. The methylation patterns of 144 non-small-cell lung cancer (NSCLC) and 7 healthy control formalin-fixed paraffin-embedded (FFPE) samples were analyzed to evaluate the applicability of the putative diagnostic markers. Statistically significant changes in methylation levels are shown for TERT and WT1 . Furthermore, 12 NSCLC and two benign lung cell lines were characterized for promoter methylation. The in vitro tests involved a comparison of promoter methylation in 2D and 3D cultures, as well as therapeutic tests investigating the impact of CDH1/ CDKN2Ap16 / RASSF1A /TERT/WT1 promoter methylation on sensitivity to tyrosine kinase inhibitor (TKI) and DNA methyl-transferase inhibitor (DNMTI) treatments. We conclude that the selected markers have potential and putative impacts as diagnostic or even predictive marker genes, although a closer examination of the resulting protein expression and pathway regulation is needed., Competing Interests: The authors declare no conflict of interest.
- Published
- 2020
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