Dynamics of LINE-1 retrotransposon methylation levels in circulating DNA from lung cancer patients undergoing antitumor therapy

A. A. Ponomaryova, N. V. Cherdyntseva, N. V. Cherdyntseva, A. A. Bondar, A. Y. Dobrodeev, A. A. Zavyalov, S. A. Tuzikov, V. V. Vlassov, E. L. Choinzonov, P. P. Laktionov, P. P. Laktionov, E. Y. Rykova, E. Y. Rykova

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    © 2017, Pleiades Publishing, Inc. Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.
    Original languageEnglish
    Pages (from-to)549-554
    Number of pages6
    JournalMolecular Biology
    Volume51
    Issue number4
    DOIs
    Publication statusPublished - 1 Jul 2017

    Fingerprint

    Retroelements
    Methylation
    Lung Neoplasms
    DNA
    Plasma Cells
    Blood Cells
    Therapeutics
    Neoplasms
    DNA Methylation
    Edetic Acid
    Trypsin
    Phosphates
    Drug Therapy
    Polymerase Chain Reaction
    Genes

    Keywords

    • aberrant methylation
    • antitumor therapy
    • circulating DNA
    • LINE-1 retrotransposons
    • lung cancer
    • prognosis

    Cite this

    Ponomaryova, A. A., Cherdyntseva, N. V., Cherdyntseva, N. V., Bondar, A. A., Dobrodeev, A. Y., Zavyalov, A. A., ... Rykova, E. Y. (2017). Dynamics of LINE-1 retrotransposon methylation levels in circulating DNA from lung cancer patients undergoing antitumor therapy. Molecular Biology, 51(4), 549-554. https://doi.org/10.1134/S0026893317040148

    Dynamics of LINE-1 retrotransposon methylation levels in circulating DNA from lung cancer patients undergoing antitumor therapy. / Ponomaryova, A. A.; Cherdyntseva, N. V.; Cherdyntseva, N. V.; Bondar, A. A.; Dobrodeev, A. Y.; Zavyalov, A. A.; Tuzikov, S. A.; Vlassov, V. V.; Choinzonov, E. L.; Laktionov, P. P.; Laktionov, P. P.; Rykova, E. Y.; Rykova, E. Y.

    In: Molecular Biology, Vol. 51, No. 4, 01.07.2017, p. 549-554.

    Research output: Contribution to journalArticle

    Ponomaryova, AA, Cherdyntseva, NV, Cherdyntseva, NV, Bondar, AA, Dobrodeev, AY, Zavyalov, AA, Tuzikov, SA, Vlassov, VV, Choinzonov, EL, Laktionov, PP, Laktionov, PP, Rykova, EY & Rykova, EY 2017, 'Dynamics of LINE-1 retrotransposon methylation levels in circulating DNA from lung cancer patients undergoing antitumor therapy', Molecular Biology, vol. 51, no. 4, pp. 549-554. https://doi.org/10.1134/S0026893317040148
    Ponomaryova AA, Cherdyntseva NV, Cherdyntseva NV, Bondar AA, Dobrodeev AY, Zavyalov AA et al. Dynamics of LINE-1 retrotransposon methylation levels in circulating DNA from lung cancer patients undergoing antitumor therapy. Molecular Biology. 2017 Jul 1;51(4):549-554. https://doi.org/10.1134/S0026893317040148
    Ponomaryova, A. A. ; Cherdyntseva, N. V. ; Cherdyntseva, N. V. ; Bondar, A. A. ; Dobrodeev, A. Y. ; Zavyalov, A. A. ; Tuzikov, S. A. ; Vlassov, V. V. ; Choinzonov, E. L. ; Laktionov, P. P. ; Laktionov, P. P. ; Rykova, E. Y. ; Rykova, E. Y. / Dynamics of LINE-1 retrotransposon methylation levels in circulating DNA from lung cancer patients undergoing antitumor therapy. In: Molecular Biology. 2017 ; Vol. 51, No. 4. pp. 549-554.
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    AU - Ponomaryova, A. A.

    AU - Cherdyntseva, N. V.

    AU - Cherdyntseva, N. V.

    AU - Bondar, A. A.

    AU - Dobrodeev, A. Y.

    AU - Zavyalov, A. A.

    AU - Tuzikov, S. A.

    AU - Vlassov, V. V.

    AU - Choinzonov, E. L.

    AU - Laktionov, P. P.

    AU - Laktionov, P. P.

    AU - Rykova, E. Y.

    AU - Rykova, E. Y.

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    N2 - © 2017, Pleiades Publishing, Inc. Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.

    AB - © 2017, Pleiades Publishing, Inc. Malignant cell transformation is accompanied with abnormal DNA methylation, such as the hypermethylation of certain gene promoters and hypomethylation of retrotransposons. In particular, the hypomethylation of the human-specific family of LINE-1 retrotransposons was observed in lung cancer tissues. It is also known that the circulating DNA (cirDNA) of blood plasma and cell-surface-bound circulating DNA (csb-cirDNA) of cancer patients accumulate tumor-specific aberrantly methylated DNA fragments, which are currently considered to be valuable cancer markers. This work compares LINE-1 retrotransposon methylation patterns in cirDNA of 16 lung cancer patients before and after treatment. CirDNA was isolated from blood plasma, and csb-cirDNA fractions were obtained by successive elution with EDTA-containing phosphate buffered saline and trypsin. Concentrations of methylated LINE-1 region 1 copies (LINE-1-met) were assayed by real-time methylation-specific PCR. LINE-1 methylation levels were normalized to the concentration of LINE-1 region 2, which was independent of the methylation status (LINE-1-Ind). The concentrations of LINE-1-met and LINE-1-Ind in csb-cirDNA of lung cancer patients exhibited correlations before treatment (r = 0.54), after chemotherapy (r = 0.72), and after surgery (r = 0.83) (P < 0.05, Spearman rank test). In the total group of patients, the level of LINE-1 methylation (determined as the LINE-1-met/LINE-1-Ind ratio) was shown to increase significantly during the follow-up after chemotherapy (P < 0.05, paired t test) and after surgery compared to the level of methylation before treatment (P < 0.05, paired t test). The revealed association between the level of LINE-1 methylation and the effect of antitumor therapy was more pronounced in squamous cell lung cancer than in adenocarcinoma (P < 0.05 and P > 0.05, respectively). These results suggest a need for the further investigation of dynamic changes in levels of LINE-1 methylation depending on the antitumor therapy.

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