Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients

Ildar V. Gainetdinov; Kristina Yu Kapitskaya; Elena Yu Rykova; Anastasia A. Ponomaryova; Nadezda V. Cherdyntseva; Valentin V. Vlassov; Pavel P. Laktionov; Tatyana L. Azhikina

doi:10.1016/j.lungcan.2016.07.005

Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients

Ildar V. Gainetdinov, Kristina Yu Kapitskaya, Elena Yu Rykova, Anastasia A. Ponomaryova, Nadezda V. Cherdyntseva, Valentin V. Vlassov, Pavel P. Laktionov, Tatyana L. Azhikina

Biology and Genomics

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	127-130
Number of pages	4
Journal	Lung Cancer
Volume	99
DOIs	https://doi.org/10.1016/j.lungcan.2016.07.005
State	Published - Sep 1 2016

Keywords

Circulating DNA
DNA methylation
L1Hs
LINE-1
Lung cancer
MIRA

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

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10.1016/j.lungcan.2016.07.005

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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.",

keywords = "Circulating DNA, DNA methylation, L1Hs, LINE-1, Lung cancer, MIRA",

author = "Gainetdinov, {Ildar V.} and Kapitskaya, {Kristina Yu} and Rykova, {Elena Yu} and Ponomaryova, {Anastasia A.} and Cherdyntseva, {Nadezda V.} and Vlassov, {Valentin V.} and Laktionov, {Pavel P.} and Azhikina, {Tatyana L.}",

note = "Funding Information: The study was supported by the fundamental research program of the Presidium of the Russian Academy of Sciences “Fundamental research for the development of biomedical technologies” ( 2014-208 ), the program of the Presidium of the Russian Academy of Sciences “Molecular and Cellular Biology” and the post-doctoral program of TPU. Publisher Copyright: {\textcopyright} 2016 Elsevier Ireland Ltd",

year = "2016",

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doi = "10.1016/j.lungcan.2016.07.005",

language = "English (US)",

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T1 - Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients

AU - Gainetdinov, Ildar V.

AU - Kapitskaya, Kristina Yu

AU - Rykova, Elena Yu

AU - Ponomaryova, Anastasia A.

AU - Cherdyntseva, Nadezda V.

AU - Vlassov, Valentin V.

AU - Laktionov, Pavel P.

AU - Azhikina, Tatyana L.

N1 - Funding Information: The study was supported by the fundamental research program of the Presidium of the Russian Academy of Sciences “Fundamental research for the development of biomedical technologies” ( 2014-208 ), the program of the Presidium of the Russian Academy of Sciences “Molecular and Cellular Biology” and the post-doctoral program of TPU. Publisher Copyright: © 2016 Elsevier Ireland Ltd

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - Circulating DNA

KW - DNA methylation

KW - L1Hs

KW - LINE-1

KW - Lung cancer

KW - MIRA

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EP - 130

JO - Lung Cancer

JF - Lung Cancer

ER -

Hypomethylation of human-specific family of LINE-1 retrotransposons in circulating DNA of lung cancer patients

Abstract

Keywords

ASJC Scopus subject areas

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