title: Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients.
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.
authors: Department of Genetics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. Electronic address: ildargv@gmail.com.
authors: Ildar V
authors: IV
authors: Gainetdinov
authors: Department of Genetics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. Electronic address: kapitskaya@gmail.com.
authors: Kristina Yu
authors: KY
authors: Kapitskaya
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk State, Russia. Electronic address: rykova@niboch.nsc.ru.
authors: Elena Yu
authors: EY
authors: Rykova
authors: Tomsk Cancer Research Institute, National Research Tomsk Polytechnic University, Tomsk, Russia. Electronic address: anastasia-ponomaryova@rambler.ru.
authors: Anastasia A
authors: AA
authors: Ponomaryova
authors: Tomsk Cancer Research Institute, National Research Tomsk State University, Tomsk, Russia. Electronic address: nvch@oncology.tomsk.ru.
authors: Nadezda V
authors: NV
authors: Cherdyntseva
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. Electronic address: vvv@niboch.nsc.ru.
authors: Valentin V
authors: VV
authors: Vlassov
authors: Institute of Chemical Biology and Fundamental Medicine SB RAS, Academician E.N. Meshalkin Novosibirsk Research Institute of Circulation Pathology, Novosibirsk, Russia Technical University, Novosibirsk, Russia. Electronic address: lakt@niboch.nsc.ru.
authors: Pavel P
authors: PP
authors: Laktionov
authors: Department of Genetics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. Electronic address: tatazhik@ibch.ru.
authors: Tatyana L
authors: TL
authors: Azhikina
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm
keywords: Circulating DNA; DNA methylation; L1Hs; LINE-1; Lung cancer; MIRA