Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients. (September 2016)

• Record Type: Journal Article
• Authors: Gainetdinov, Ildar V.; Kapitskaya, Kristina Yu.; Rykova, Elena Yu.; Ponomaryova, Anastasia A.; Cherdyntseva, Nadezda V.; Vlassov, Valentin V.; Laktionov, Pavel P.; Azhikina, Tatyana L.
• Is Part Of: Lung cancer. Volume 99(2016)
• Page Start: 127
• Page End: 130
• Publication Date: 2016-09
• Subjects: MSP methyl-specific PCR -- csbDNA cell-surface-bound fraction of circulating DNA -- cfDNA cell-free circulating DNA; Lung cancer -- Circulating DNA -- DNA methylation -- LINE-1 -- L1Hs -- MIRA; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2016.07.005
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: MIRA detects hypomethylation of LINE-1 promoters in csbDNA of lung cancer patients. Level of hypomethylation is more pronounced for human-specific L1Hs family. ROC-curve analysis supports MIRA assay as a promising diagnostic tool. Abstract: Circulating DNA has recently gained attention as a fast and non-invasive way to assess tumor biomarkers. Since hypomethylation of LINE-1 repetitive elements was described as one of the key hallmarks of tumorigenesis, we aimed to establish whether the methylation level of LINE-1 retrotransposons changes in cell-surface-bound fraction of circulating DNA (csbDNA) of lung cancer patients. Methylated CpG Island Recovery Assay (MIRA) coupled to qPCR-based quantitation was performed to assess integral methylation level of LINE-1 promoters in csbDNA of non-small cell lung cancer patients (n = 56) and healthy controls (n = 44). Deep sequencing of amplicons revealed that hypomethylation of LINE-1 promoters in csbDNA of lung cancer patients is more pronounced for the human-specific L1Hs family. Statistical analysis demonstrates significant difference in LINE-1 promoter methylation index between cancer patients and healthy individuals (ROC-curve analysis: n = 100, AUC = 0.69, p = 0.0012) and supports the feasibility of MIRA as a promising non-invasive approach.