LAUSR

Background Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. NSCLCs are mainly classified adenocarcinoma and squamous cell carcinoma. It seems more and more obvious that specific molecular analyses are necessary to elucidate the complexity of clinically relevant phenotypes which determine the lung carcinogenesis. This includes the role of microRNAs (miRNAs) in the disease, involved in the complexity of gene expression regulation. Different modulator mechanisms are involved in the biogenesis and function of miRNAs, one of them is DNA methylation. Alterations in these mechanisms may contribute to the tumor genesis and progression. The purpose of this study was to assess miRNA methylation patterns in patients with NSCLC to study the potential of coordinate regulation of miRNAs as a relevant mechanism involved in this pathogenesis. Materials and Methods DNA methylation of gene clusters was analyzed by Illumina 70 subjects. The samples were divided into two cohorts. A first cohort constituted from 47 patients who had undergone surgical resection for clinical early stage NSCLC. A second group from 23 subjects was used as health cohort. DNA was extracted using the QIAamp DNA Mini Kit. For each assay, 500 ng of DNA was treated with sodium bisulfate using EZ DNA Methylation™ Kit and cleaned with ZR-96 DNA Clean-up Kit™, before standard Illumina amplification, hybridization, and imaging steps. Methylation data were processed using the RnBeads R package. Results We identified two clusters clearly corregulated by methylation in lung cancer, involving 49 miRNAs differentially hypomethylated in tumor samples respect to control tissue. Some of these miRNAs have been implicated in several pathways in cancer. Conclusions Our results strongly imply hypomethylation of two miRNA clusters, which represent key targets in unravelling of the mechanism of lung tumorigenesis. Citation Format: Irene Ferrer, Ana Salinas, Angela Marrugal, Jon Zugazagoitia, Amancio Carnero, Luis Paz-Ares, Sonia Molina-Pinelo. Coordinated regulation of several microRNAs in lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4362. doi:10.1158/1538-7445.AM2017-4362