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

被引：23

作者：

Tanas, Alexander S. ^{[1
,2
]}

Sigin, Vladimir O. ^{[1
]}

Kalinkin, Alexey, I ^{[1
,3
]}

Litviakov, Nikolai, V ^{[4
]}

Slonimskaya, Elena M. ^{[5
]}

Ibragimova, Marina K. ^{[4
]}

Ignatova, Ekaterina O. ^{[6
]}

Simonova, Olga A. ^{[1
]}

Kuznetsova, Ekaterina B. ^{[1
,3
]}

Kekeeva, Tatiana, V ^{[1
]}

Larin, Sergey S. ^{[7
,8
]}

Poddubskaya, Elena, V ^{[9
,10
]}

Trotsenko, Ivan D. ^{[11
]}

Rudenko, Viktoria V. ^{[1
]}

Karandasheva, Kristina O. ^{[1
]}

Petrova, Kseniya D. ^{[1
,12
]}

Tsyganov, Matvey M. ^{[4
]}

Deryusheva, Irina, V ^{[4
]}

Kazantseva, Polina, V ^{[5
]}

Doroshenko, Artem, V ^{[5
]}

Tarabanovskaya, Natalia A. ^{[5
]}

Chesnokova, Galina G. ^{[1
]}

Sekacheva, Marina, I ^{[9
]}

Nemtsova, Marina, V ^{[1
,3
]}

Izheyskaya, Vera L. ^{[1
]}

Kutsev, Sergey, I ^{[1
,2
]}

Zaletaev, Dmitry, V ^{[1
,2
,3
]}

Strelnikov, Vladimir V. ^{[1
,2
]}

机构：

[1] Res Ctr Med Genet, Epigenet Lab, Moscow, Russia

[2] Pirogov Russian Natl Res Med Univ, Mol & Cell Genet Dept, Moscow, Russia

[3] IM Sechenov First Moscow State Med Univ, Med Genet Lab, Sechenov Univ, Moscow, Russia

[4] Tomsk Natl Res Med Ctr, Canc Res Inst, Lab Oncovirol, Tomsk, Russia

[5] Tomsk Natl Res Med Ctr, Canc Res Inst, Dept Gen Oncol, Tomsk, Russia

[6] Minist Hlth Russian Federat, Fed State Budgetary Inst, NN Blokhin Natl Med Res Ctr Oncol, Clin Pharmacol & Chemotherapy, Moscow, Russia

[7] Inst Gene Biol, Gene Therapy Lab, Moscow, Russia

[8] Fed Sci Clin Ctr Pediat Hematol Oncol Immunol, Mol Immunol Lab, Moscow, Russia

[9] IM Sechenov First Moscow State Med Univ, Sechenov Univ, Clin Personalized Med, Moscow, Russia

[10] VitaMed LLC, Moscow, Russia

[11] RUDN Univ, Inst Med, Moscow, Russia

[12] State Univ, Moscow Inst Phys & Technol, Dept Biol & Med Phys, Dolgoprudnyi, Moscow Region, Russia

来源：

EPIGENOMICS | 2019年 / 11卷 / 06期

基金：

俄罗斯科学基金会;

关键词：

5-fluorouracil; adenylate cyclase pathway; breast cancer; cancer cell lines; DNA methylation; DNA methylotype; leukotriene receptors; reduced representation bisulfite sequencing; resveratrol; XmaI-RRBS; TUMOR-SUPPRESSOR GENES; DNA METHYLATION; CPG ISLANDS; EXPRESSION; BIOMARKER; PROFILE;

D O I：

10.2217/epi-2018-0213

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：605 / 617

页数：13

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