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. 2019 May;11(6):605-617.
doi: 10.2217/epi-2018-0213. Epub 2019 Feb 7.

Genome-wide methylotyping resolves breast cancer epigenetic heterogeneity and suggests novel therapeutic perspectives

Alexander S Tanas  1   2 , Vladimir O Sigin  1 , Alexey I Kalinkin  1   3 , Nikolai V Litviakov  4 , Elena M Slonimskaya  5 , Marina K Ibragimova  4 , Ekaterina O Ignatova  6 , Olga A Simonova  1 , Ekaterina B Kuznetsova  1   3 , Tatiana V Kekeeva  1 , Sergey S Larin  7   8 , Elena V Poddubskaya  9   10 , Ivan D Trotsenko  11 , Viktoria V Rudenko  1 , Kristina O Karandasheva  1 , Kseniya D Petrova  1   12 , Matvey M Tsyganov  4 , Irina V Deryusheva  4 , Polina V Kazantseva  5 , Artem V Doroshenko  5 , Natalia A Tarabanovskaya  5 , Galina G Chesnokova  1 , Marina I Sekacheva  9 , Marina V Nemtsova  1   3 , Vera L Izhevskaya  1 , Sergey I Kutsev  1   2 , Dmitry V Zaletaev  1   2   3 , Vladimir V Strelnikov  1   2
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Free article

Genome-wide methylotyping resolves breast cancer epigenetic heterogeneity and suggests novel therapeutic perspectives

Alexander S Tanas et al. Epigenomics. 2019 May.
Free article

Abstract

Aim: To provide a breast cancer (BC) methylotype classification by genome-wide CpG islands bisulfite DNA sequencing. Materials & methods: XmaI-reduced representation bisulfite sequencing DNA methylation sequencing method was used to profile DNA methylation of 110 BC samples and 6 normal breast samples. Intrinsic DNA methylation BC subtypes were elicited by unsupervised hierarchical cluster analysis, and cluster-specific differentially methylated genes were identified. Results & conclusion: Overall, six distinct BC methylotypes were identified. BC cell lines constitute a separate group extremely highly methylated at the CpG islands. In turn, primary BC samples segregate into two major subtypes, highly and moderately methylated. Highly and moderately methylated superclusters, each incorporate three distinct epigenomic BC clusters with specific features, suggesting novel perspectives for personalized therapy.

Keywords: 5-fluorouracil; DNA methylation; DNA methylotype; XmaI-RRBS; adenylate cyclase pathway; breast cancer; cancer cell lines; leukotriene receptors; reduced representation bisulfite sequencing; resveratrol.

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