Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
| Main Authors: | Laplana, Marina, Bieg, Matthias, Faltus, Christian, Melnik, Svitlana, Bogatyrova, Olga, Gu, Zuguang, Muley, Thomas, Meister, Michael, Dienemann, Hendrik, Herpel, Esther, Amos, Christopher I., Schlesner, Matthias, Eils, Roland, Plass, Christoph, Risch, Angela |
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| Format: | Article Journal |
| Bahasa: | eng |
| Terbitan: |
, 2020
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/4327115 |
Daftar Isi:
- Objectives: Genome-wide association studies (GWAS) have identified SNPs linked with lung cancer risk. Our aim was to discover the genes, non-coding RNAs and regulatory elements within GWAS-identified risk regions that are deregulated in non-small cell lung carcinoma (NSCLC) to identify novel, clinically targetable genes and mechanisms in carcinogenesis. Materials and Methods: A targeted bisulfite-sequencing approach was used to comprehensively investigate DNA methylation changes occurring within lung cancer risk regions in 17 NSCLC and adjacent normal tissue pairs. Results: We report differences in differentially methylated regions between adenocarcinoma and squamous cell carcinoma. Among minimal regions found to be differentially methylated in at least 50% of the patients, 7 candidates were replicated in 2 independent cohorts (n=27 and n=87) and the potential of 6 as methylation dependent regulatory elements was confirmed by functional assays. Conclusion: This study contributes to understanding the pathways implicated in lung cancer initiation and progression, and provides new potential targets for cancer treatment.