Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA

Malignant cell transformation is accompanied by two processes of DNA methylation changes: promoter hypermethylation of specific genes and hypomethylation of retrotransposons. The composition of circulating DNA (cirDNA) from plasma and cell-surface-bound circulating DNA (csb- cirDNA) was shown earlie...

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Main Authors: A. A. Ponomaryova, Е. Y. Rykova, N. V. Cherdyntseva, A. A. Bondar, A. Y. Dobrodeev, A. A. Zavyalov, S. A. Tuzikov, L. O. Bryzgalov, T. I. Merkulova, V. V. Vlassov, P. P. Laktionov
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2015-07-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/357
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author A. A. Ponomaryova
Е. Y. Rykova
N. V. Cherdyntseva
A. A. Bondar
A. Y. Dobrodeev
A. A. Zavyalov
S. A. Tuzikov
L. O. Bryzgalov
T. I. Merkulova
V. V. Vlassov
P. P. Laktionov
author_facet A. A. Ponomaryova
Е. Y. Rykova
N. V. Cherdyntseva
A. A. Bondar
A. Y. Dobrodeev
A. A. Zavyalov
S. A. Tuzikov
L. O. Bryzgalov
T. I. Merkulova
V. V. Vlassov
P. P. Laktionov
author_sort A. A. Ponomaryova
collection DOAJ
description Malignant cell transformation is accompanied by two processes of DNA methylation changes: promoter hypermethylation of specific genes and hypomethylation of retrotransposons. The composition of circulating DNA (cirDNA) from plasma and cell-surface-bound circulating DNA (csb- cirDNA) was shown earlier to be altered in the blood of cancer patients due to accumulation of tumor- specific aberrantly methylated DNA fragments, which are currently considered valuable cancer markers. The present study compares LINE-1 retrotransposon methylation patterns in plasma cirDNA and csb- cirDNA from 21 untreated lung cancer patients (LC) and 23 healthy donors. Concentrations of methylated LINE-1 region 1 copies (LINE-1met) were assayed by real-time methylation-specific PCR. In order to normalize the LINE-1 methylation level, the LINE-1 region 2 concentration was evaluated, which was independent of the methylation status (LINE-1Ind). The LINE-1met concentration in csb-cirDNA tended to decrease (by a factor of 1.4) in blood from LC patients in comparison to healthy donors (Mann- Whitney test, P=0.16). The LINE-1Ind concentration in csb-cirDNA (methylation-independent) was found to be threefold lower in LC patients and fourfold lower in patients with adenocarcinoma than in healthy donors. That is why, along with the expected decrease in LINE-1met concentration in csb-cirDNA, we recorded an unexpected statistically significant increase of the LINE-1 methylation index determined as (LINE-1met/LINE-1Ind) due to the profound LINE-1Ind decrease. Plasma cirDNA demonstrated no difference in the LINE-1 methylation index (LINE-1met/LINE-1Ind) between LC patients and healthy donors (Mann-Whitney test, P = 0.40). The data obtained agree with our earlier results, which showed that csb-cirDNA was a highly informative material for lung cancer diagnostics.
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publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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spelling doaj-art-f4b173a92e4c468e9f12fce41c614e522025-02-01T09:58:01ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592015-07-0119114415010.18699/VJ15.018336Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNAA. A. Ponomaryova0Е. Y. Rykova1N. V. Cherdyntseva2A. A. Bondar3A. Y. Dobrodeev4A. A. Zavyalov5S. A. Tuzikov6L. O. Bryzgalov7T. I. Merkulova8V. V. Vlassov9P. P. Laktionov10Tomsk Cancer Research Institute, Tomsk, Russia The National Research Tomsk Polytechnic University, Tomsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, RussiaTomsk Cancer Research Institute, Tomsk, Russia National Research Tomsk State University, Tomsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, RussiaTomsk Cancer Research Institute, Tomsk, RussiaTomsk Cancer Research Institute, Tomsk, RussiaTomsk Cancer Research Institute, Tomsk, RussiaInstitute of Cytology and Genetics SB RAS, NovosibirskInstitute of Cytology and Genetics SB RAS, NovosibirskInstitute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, RussiaMalignant cell transformation is accompanied by two processes of DNA methylation changes: promoter hypermethylation of specific genes and hypomethylation of retrotransposons. The composition of circulating DNA (cirDNA) from plasma and cell-surface-bound circulating DNA (csb- cirDNA) was shown earlier to be altered in the blood of cancer patients due to accumulation of tumor- specific aberrantly methylated DNA fragments, which are currently considered valuable cancer markers. The present study compares LINE-1 retrotransposon methylation patterns in plasma cirDNA and csb- cirDNA from 21 untreated lung cancer patients (LC) and 23 healthy donors. Concentrations of methylated LINE-1 region 1 copies (LINE-1met) were assayed by real-time methylation-specific PCR. In order to normalize the LINE-1 methylation level, the LINE-1 region 2 concentration was evaluated, which was independent of the methylation status (LINE-1Ind). The LINE-1met concentration in csb-cirDNA tended to decrease (by a factor of 1.4) in blood from LC patients in comparison to healthy donors (Mann- Whitney test, P=0.16). The LINE-1Ind concentration in csb-cirDNA (methylation-independent) was found to be threefold lower in LC patients and fourfold lower in patients with adenocarcinoma than in healthy donors. That is why, along with the expected decrease in LINE-1met concentration in csb-cirDNA, we recorded an unexpected statistically significant increase of the LINE-1 methylation index determined as (LINE-1met/LINE-1Ind) due to the profound LINE-1Ind decrease. Plasma cirDNA demonstrated no difference in the LINE-1 methylation index (LINE-1met/LINE-1Ind) between LC patients and healthy donors (Mann-Whitney test, P = 0.40). The data obtained agree with our earlier results, which showed that csb-cirDNA was a highly informative material for lung cancer diagnostics.https://vavilov.elpub.ru/jour/article/view/357blood-circulating dnaaberrant methylationline-1 retrotransposonsdiagnosticslung cancer
spellingShingle A. A. Ponomaryova
Е. Y. Rykova
N. V. Cherdyntseva
A. A. Bondar
A. Y. Dobrodeev
A. A. Zavyalov
S. A. Tuzikov
L. O. Bryzgalov
T. I. Merkulova
V. V. Vlassov
P. P. Laktionov
Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA
Вавиловский журнал генетики и селекции
blood-circulating dna
aberrant methylation
line-1 retrotransposons
diagnostics
lung cancer
title Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA
title_full Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA
title_fullStr Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA
title_full_unstemmed Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA
title_short Epigenetic «probes» for lung cancer monitoring: LINE-1 methylation pattern in blood- circulating DNA
title_sort epigenetic probes for lung cancer monitoring line 1 methylation pattern in blood circulating dna
topic blood-circulating dna
aberrant methylation
line-1 retrotransposons
diagnostics
lung cancer
url https://vavilov.elpub.ru/jour/article/view/357
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