Identification of regulatory SNPs associated with genetic modifications in lung adenocarcinoma.

Background: Although much research effort has been devoted to elucidating lung cancer, the molecular mechanism of tumorigenesis still remains unclear. A major challenge to improve the understanding of lung cancer is the difficulty of identifying reproducible differentially expressed genes across independent studies, due to their low consistency. To enhance the reproducibility of the findings, an integrated analysis was performed to identify regulatory SNPs. Thirty-two pairs of tumor and adjacent normal lung tissue specimens were analyzed using Affymetrix U133plus2.0, Affymetrix SNP 6.0, and Illumina Infinium Methylation microarrays. Copy number variations (CNVs) and methylation alterations were analyzed and paired t-tests were used to identify differentially expressed genes.
Results: A total of 505 differentially expressed genes were identified, and their dysregulated patterns moderately correlated with CNVs and methylation alterations based on the hierarchical clustering analysis. Subsequently, three statistical approaches were performed to explore regulatory SNPs, which revealed that the genotypes of 551 and 66 SNPs were associated with CNV and changes in methylation, respectively. Among them, downstream transcriptional dysregulation was observed in 9 SNPs for CNVs and 4 SNPs for methylation alterations.
Conclusions: In summary, these identified SNPs concurrently showed the same direction of gene expression changes with genetic modifications, suggesting their pivotal roles in the genome for non-smoking women with lung adenocarcinoma.