Significant Association Among the Epigenetic Alterations in EGFR and ALK Genes and Non–Small Cell Lung Cancer: A Prospective Emerging Molecular Biomarker

Abstract

Background

Non–small cell lung cancer (NSCLC) is increasingly recognized as a heterogeneous set of diseases at the molecular level, and these differences likely could drive therapeutic decision-making. The anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) genes are two key oncogenes of tyrosine kinase that their expression is increased in lung cancer and activates their downstream signaling cascade. These two genes have been identified as therapeutic targets, and targeted therapies for these genes by tyrosine kinase inhibitors have been approved by the FDA.

Objective

We aimed to elucidate the epigenetic alterations in ALK and EGFR genes in NSCLC patients.

Methods

Fifty tissue samples of the paired NSCLC samples and adjacent normal tissues were evaluated by methylation-specific polymerase chain reaction (MS-PCR). Subsequently, the methylation status of the EGFR and ALK genes promoter was examined by bioinformatics tools such as UCSC, GTEx portal, and iMETHYL servers.

Results

There was a significant difference in the methylation pattern of EGFR (Region II) (p = 0.02) between the case and control groups and also that patients who were methylated in this region of the EGFR promoter had a higher stage than non-methylated patients, which was statistically significant (p = 0.03).

Conclusion

We analyzed methylation changes of EGFR and ALK genes in patients suffering from NSCLC. Alteration of EGFR gene methylation pattern could play an important role in the pathogenesis of NSCLC. To delineate the potential role of ALK somatic alterations, further investigations are warranted.