1529P - DLK1-DIO3 imprinted cluster in lung cancer

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Translational Research
Presenter Alvaro Quintanal
Citation Annals of Oncology (2016) 27 (6): 526-544. 10.1093/annonc/mdw392
Authors A. Quintanal1, A. Salinas2, R. Suarez1, R. Meléndez2, A. Carnero3, L. Paz-Ares1, S. Molina-Pinelo1
  • 1Medical Oncology, Hospital Universitario Doce de Octubre, 28041 - Madrid/ES
  • 2Instituto De Biomedicina De Sevilla, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 3Molecular Oncology Laboratory, IBIS/CSIC/US, 41013 - Sevilla/ES

Abstract

Background

According to classical Mendelian laws, the majority of genes in a human cell are inherited in two functionally equivalent parental copies. However, there is a small subset of genes with one turned-off copy in a parent-of-origin-dependent manne. This phenomenon, known as genomic imprinting, is an epigenetic process that involves monoallelic expression. Some genes are imprinted across the complete genome sequence, but the vast majority of imprinted genes are clustered. In this sense, the DLK1-DIO3 imprinted cluster is located on chromosome 14q32.2. This region includes protein-coding genes (DLK1, RTL1 and DIO3), long non-coding RNAs (MEG3, MEG8, MEG9 and LINC00524), two large clusters of miRNAs, two families of small nucleolar RNAs (SNORD113 and SNORD114) and several pseudogenes. Aberrations involving some components of the DLK1-DIO3 cluster have been linked to pathological processes. The purpose of this study was to assess the role of the DLK1-DIO3 cluster in non-small cell lung cancer.

Methods

DNA methylation of gene clusters was analyzed by Illumina in tumour and matched control (healthy) tissue from 47 patients with lung cancer. 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

Patients with lung cancer showed three deregulated protein-coding genes: one was hypermethylated (DIO3) and two were hypomethylated (DLK1 and RTL1). Statistically significant differences (adjusted p-value 

Conclusions

Our results strongly imply that hypomethylation of this cluster may be a key target in unravelling of the mechanism of lung cancer.

Clinical trial identification

Legal entity responsible for the study

Fundación para la Investigación Biomédica del Hospital Universitario 12 de Octubre

Funding

SMP is funded by Fondo de Investigación Sanitaria (CD1100153), Consejería de Salud y Bienestar Social (PI2009-0224 and PI-0046-2012), and Fundación Mutua Madrileña (2014). LPA is funded by Fondo de Investigación Sanitaria (PI1102688 and 1401964) and RTICC (R12/0036/0028). IF is funded by Fundación AECC.

Disclosure

All authors have declared no conflicts of interest.