1. Genome-wide methylotyping resolves breast cancer epigenetic heterogeneity and suggests novel therapeutic perspectives.
- Author
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Tanas AS, Sigin VO, Kalinkin AI, Litviakov NV, Slonimskaya EM, Ibragimova MK, Ignatova EO, Simonova OA, Kuznetsova EB, Kekeeva TV, Larin SS, Poddubskaya EV, Trotsenko ID, Rudenko VV, Karandasheva KO, Petrova KD, Tsyganov MM, Deryusheva IV, Kazantseva PV, Doroshenko AV, Tarabanovskaya NA, Chesnokova GG, Sekacheva MI, Nemtsova MV, Izhevskaya VL, Kutsev SI, Zaletaev DV, and Strelnikov VV
- Subjects
- Breast Neoplasms therapy, Cell Line, Tumor, Cluster Analysis, Epigenesis, Genetic, Female, Humans, Breast Neoplasms genetics, DNA Methylation
- 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.
- Published
- 2019
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