Genes and telomeric proteins as biomarkers in non-small cell lung cancer (NSCLC)

Abstract

According to the World Health Organization lung cancer has a high mortality rate causing >1.5 million deaths per year. Efforts have been made to identify molecular markers associated to the development and progression of non-small cell lung carcinoma (NSCLS), which corresponds to ~85% of lung cancer cases, with the aim to discover new therapeutic targets. Among these targets, telomeres have a potential clinical application due to their role in maintaining genomic stability. Telomeres are maintained by the action of the ribonucleoprotein telomerase, which has two main components: the protein telomerase reverse transcriptase (TERT) and the non coding telomerase RNA component (TERC), which bears the template sequence for the telomere repeat. In humans telomeres are nucleoprotein complexes composed by repetitive DNA associated with proteins of the shelterin complex. Recent data show that TERT, and some of the shelterin components are involved in the development of NSCLC. However, due to controversial data about the correlation between alterations in telomeric function and lung cancer development deeper studies are required. The aim of the present project is to verify among the telomeric proteins and the telomerase complex new molecular markers specific for NSCLC tumors. In order to achieve this goal we will search RNAseq libraries, obtained from tumor and normal tissue samples of NSCLC patients, for genes associated directly and indirectly with the telomeric machinery. The results will be validated using RT-qPC gene expression analysis. Additionally, we will evaluate the restriction profile of leucocyte telomeres and estimate telomere length from NSCLC patients and compare with normal controls, using respectively southern blot and flow-FISH analysis. (AU)