# Characterization of DNA Methylation Episignatures for Radon-Induced Lung Cancer

## TL;DR

This study identifies DNA methylation changes linked to radon-induced lung cancer, highlighting potential biomarkers and therapeutic targets.

## Contribution

The study characterizes specific DNA methylation episignatures in blood and lung tissue associated with radon-induced lung cancer.

## Key findings

- Radon exposure alters DNA methylation patterns in both blood and lung tissues.
- DNAm episignatures of MAPK10, PLCG1, PLCβ3, and PIK3R2 are consistently affected by radon exposure.
- Radon exposure promotes lung cancer in a mouse model, with corresponding gene expression changes.

## Abstract

Radon (Rn) exposure has a strong association with lung cancer risk and is influenced by epigenetic modifications. To investigate the characterization of DNA methylation (DNAm) episignatures for radon-induced lung cancer, we detected the specific changes in DNAm in blood and lung tissues using reduced representation bisulfite sequencing (RRBS). We identified the differentially methylated regions (DMRs) induced by radon exposure. The bioinformatics analysis of the DMR-mapped genes revealed that pathways in cancer were affected by radon exposure. Among them, the DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 were repeated between lung tissue and blood, and validated by the MassArray. In addition, radon exposure promoted lung cancer development in the genetic engineering mouse model (GEMM), accompanied by decreased MAPK10 and increased PLCG1, PLCβ3, and PIK3R2 with mRNA and protein levels. Conclusively, radon exposure significantly changes the genomic DNAm patterns in lung tissue and blood. The DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 have a significant influence on radon-induced lung cancer. This brings a new perspective to understanding the pathways involved in radon-induced lung cancer and offers potential targets for developing blood-based biomarkers and epigenetic therapeutics.