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

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. © 2019 Alexander Tanas et al.

Authors
Tanas A.S.1, 2 , Sigin V.O.1 , Kalinkin A.I.1, 3 , Litviakov N.V.4 , Slonimskaya E.M.5 , Ibragimova M.K.4 , Ignatova E.O.6 , Simonova O.A.1 , Kuznetsova E.B.1, 3 , Kekeeva T.V.1 , Larin S.S.7, 8 , Poddubskaya E.V.9, 10 , Trotsenko I.D. 11 , Rudenko V.V.1 , Karandasheva K.O.1 , Petrova K.D.1, 12 , Tsyganov M.M.4 , Deryusheva I.V.4 , Kazantseva P.V.5 , Doroshenko A.V.5 , Tarabanovskaya N.A.5 , Chesnokova G.G.1 , Sekacheva M.I.9 , Nemtsova M.V.1, 3 , Izhevskaya V.L.1 , Kutsev S.I.1, 2 , Zaletaev D.V.1, 2, 3 , Strelnikov V.V.1, 2
Journal
Epigenomics
Publisher
Future Medicine Ltd.
Number of issue
6
Language
English
Pages
605-617
Status
Published
Link
External link
DOI
10.2217/EPI-2018-0213
Volume
11
Year
2019
Organizations
  • 1 Epigenetics Laboratory, Research Centre for Medical Genetics, Moscow, Russian Federation
  • 2 Molecular and Cell Genetics Department, Pirogov Russian National Research Medical University, Moscow, Russian Federation
  • 3 Medical Genetics Laboratory, I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russian Federation
  • 4 Laboratory of Oncovirology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russian Federation
  • 5 Department of General Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Tomsk, Russian Federation
  • 6 Clinical Pharmacology and Chemotherapy, Federal State Budgetary Institution, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russian Federation
  • 7 Gene Therapy Laboratory, Institute of Gene Biology, Moscow, Russian Federation
  • 8 Molecular Immunology Laboratory, Fed. Sci. Clinical Centre of Pediatric Hematology Oncology Immunology Named after Dmitry Rogachev, Moscow, Russian Federation
  • 9 Clinic of Personalized Medicine, I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russian Federation
  • 10 VitaMed LLC, Moscow, Russian Federation
  • 11 Institute of Medicine, RUDN University, Moscow, Russian Federation
  • 12 Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, State University, Dolgoprudny, Moscow Region, Russian Federation
Keywords
5-fluorouracil; adenylate cyclase pathway; breast cancer; cancer cell lines; DNA methylation; DNA methylotype; leukotriene receptors; reduced representation bisulfite sequencing; resveratrol; XmaI-RRBS
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