Analysis of Single Nucleotide Variants (SNVs) Induced by Exposure to PM10 in Lung Epithelial Cells Using Whole Genome Sequencing

Abstract

There are many epidemiological studies asserting that fine dust causes lung cancer, but the biological mechanism is not clear. This study was conducted to investigate the effect of PM10 (particulate matter less than 10 μm) on single nucleotide variants through whole genome sequencing in lung epithelial cancer cell lines (HCC-827, NCI-H358) that have been exposed to PM10. The two cell lines were exposed to PM10 for 15 days. We performed experimental and next generation sequencing analyses on experimental group that had been exposed to PM10 as well as an unexposed control group. After exposure to PM10, 3005 single nucleotide variants were newly identified in the NCI-H358 group, and 4402 mutations were identified in the HCC-827 group. We analyzed these single nucleotide variants with the Mutalisk program. We observed kataegis in chromosome 1 in NCI-H358 and chromosome 7 in HCC-827. In mutational signatures analysis, the COSMIC mutational signature 5 was highest in both HCC-827 and NCI-H358 groups, and each cosine similarity was 0.964 in HCC-827 and 0.979 in the NCI-H358 group. The etiology of COSMIC mutational signature 5 is unknown at present. Well-designed studies are needed to determine whether environmental factors, such as PM10, cause COSMIC mutational signature 5.