Relationship between 3p deletions and telomerase activity in non-small-cell lung cancer: prognostic implications

Abstract

3p deletions and telomerase reactivation are two of the most frequent events described in relation to non-small-cell lung cancer (NSCLC) pathogenesis. Moreover, a number of genes that map on 3p have been proposed as candidates to tumour-suppressor genes of importance in the lung cancer process. In this work, we analysed deletions at different 3p loci in relationship to telomerase activity in 66 NSCLCs obtained from patients who had suffered potentially curative surgery. Also, we evaluated prognostic implications. DNA samples were analysed for 3p deletions using five different polymorphic human dinucleotide repeat DNA markers (D3S1619 at 3p22.2, D3S3623 at 3p22.1, D3S1260 at 3p21.33, D3S3697 at 3p14.3, and D3S3722 at 3p21.2). Telomerase activity was investigated by a TRAP-based method. Possible correlations between the different molecular markers and distributions of disease-free survival were estimated. Our data revealed a significant correlation between telomerase activity and losses of heterozygosity (LOH) on D3S3697 (P ¼ 0.040), since all of the tumours showing deletion at this locus were positives for telomerase. Moreover, our results revealed clear associations with poor prognosis of patients, in the case of LOH at D3S1260 and D3S3697 (P ¼ 0.005 and 0.005, respectively). According to our data, potential repressors for telomerase may be located in chromosome 3p.

Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer

“…Both genes map in 3p (3p21.31-p21.1 and 3p21.3, respectively), and chromosome 3p deletions constitute one of the most frequent events described in relation to NSCLC pathogenesis. Previous data from our group and others [33] suggested the existence on 3p of one or several genes implicated on telomerase negative regulation.…”

Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer

“…This reactivation seems to arrest the normal loss of telomeric DNA incurred as somatic cells divide. Since continual loss of telomeric DNA is predicted to eventually limit cell proliferation, activation of telomerase in cancer cells may be an important step in the acquisition of cell immortalisation, which occurs during tumor progression [5].…”

An Update on the Other Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors

“…Iniesta et al found correlation between telomerase activity and loss of heterozygosity at position 3p14.3 [224]. Deletion at this position was also associated with poor prognosis.…”