@article{75d18b9adb8d430fa789efa074d68c9e,
title = "Promoter methylation of selected genes in non-small-cell lung cancer patients and cell lines",
abstract = "Specific gene promoter DNA methylation is becoming a powerful epigenetic biomarker in cancer diagnostics. Five genes (CDH1, CDKN2Ap16, RASSF1A, 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.",
keywords = "cyclin dependent kinase inhibitor 2A, DNA methyltransferase inhibitor, epidermal growth factor receptor, K ras protein, protein tyrosine kinase inhibitor, Ras association domain family protein 1A, telomerase reverse transcriptase, uvomorulin, WT1 protein, cadherin, CDH1 protein, human, leukocyte antigen, tumor marker, Article, bisulfite pyrosequencing, Calu-1 cell line, controlled study, DNA methylation, EC50, epigenetics, female, gene mutation, HCC2935 cell line, HCC4006 cell line, HCC827 cell line, high throughput sequencing, human tissue, IMR-90 cell line, limit of detection, major clinical study, male, MRC-5 cell line, NCI-H1437 cell line, NCI-H1975 cell line, non small cell lung cancer, personalized medicine, protein expression, three dimensional cell culture, aged, gene expression regulation, genetics, lung tumor, metabolism, middle aged, pathology, prognosis, promoter region, tumor cell culture, Aged, Antigens, CD, Biomarkers, Tumor, Cadherins, Carcinoma, Non-Small-Cell Lung, DNA Methylation, Female, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, Male, Middle Aged, Prognosis, Promoter Regions, Genetic, Tumor Cells, Cultured, Epigenetic marker, Precision medicine, NSCLC, Epigenetics, Gene Expression Regulation, Neoplastic, Biomarkers, Tumor/genetics, Lung Neoplasms/genetics, Tumor Cells, Cultured, Promoter Regions, Genetic, Antigens, CD/genetics, Cadherins/genetics, Carcinoma, Non-Small-Cell Lung/genetics",
author = "V. Sarne and S. Huter and S. Braunmueller and L. Rakob and Nico Jacobi and M. Kitzw{\"o}gerer and C. Wiesner and P. Obrist and R. Seeboeck",
note = "Funding Information: Funding: This research was funded by the {\"O}sterreichische Forschungsf{\"o}rderungsgesellschaft; Programm Talente, FEMtech Forschungsprojekte; FFG Austria, grant number 849800. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = jun,
day = "28",
doi = "10.3390/ijms21134595",
language = "English",
volume = "21",
pages = "1--22",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "13",
}
