Cell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis

被引：63

作者：

Bormann, Felix ^{[1
]}

Rodriguez-Paredes, Manuel ^{[1
]}

Lasitschka, Felix ^{[2
]}

Edelmann, Dominic ^{[3
]}

Musch, Tanja ^{[1
]}

Benner, Axel ^{[3
]}

Bergman, Yehudit ^{[4
]}

Dieter, Sebastian M. ^{[5
,6
]}

Ball, Claudia R. ^{[7
,8
]}

Glimm, Hanno ^{[7
,8
,9
,10
]}

Linhart, Heinz G. ^{[1
,11
,12
]}

Lyko, Frank ^{[1
]}

机构：

[1] German Canc Res Ctr, DKFZ ZMBH Alliance, Div Epigenet, D-69120 Heidelberg, Germany

[2] Heidelberg Univ Hosp, Inst Pathol, D-69120 Heidelberg, Germany

[3] German Canc Res Ctr, Div Biostat, D-69120 Heidelberg, Germany

[4] Hebrew Univ Jerusalem, Med Sch, Inst Med Res Israel Canada, Dept Dev Biol & Canc Res, IL-91120 Jerusalem, Israel

[5] Natl Ctr Tumor Dis NCT Heidelberg, Dept Translat Oncol, D-69120 Heidelberg, Germany

[6] German Canc Res Ctr, D-69120 Heidelberg, Germany

[7] NCT Dresden, Dept Translat Med Oncol, D-01307 Dresden, Germany

[8] DKFZ Heidelberg, D-01307 Dresden, Germany

[9] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany

[10] German Canc Consortium DKTK, D-69120 Heidelberg, Germany

[11] Klin Lindau, D-88131 Lindau, Germany

[12] Univ Hosp Freiburg, Dept Gastroenterol, D-79160 Freiburg, Germany

来源：

CELL REPORTS | 2018年 / 23卷 / 11期

关键词：

STEM-CELLS; INTEGRATIVE ANALYSIS; CANCER; DIFFERENTIATION; PHENOTYPE; BRAF; EXPRESSION; ADENOMAS; DYNAMICS; CRYPT;

D O I：

10.1016/j.celrep.2018.05.045

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Colorectal adenomas are precursor lesions of colorectal cancers and represent clonal amplifications of single cells from colonic crypts. DNA methylation patterns specify cell-type identity during cellular differentiation and, therefore, provide opportunities for the molecular analysis of tumors. We have now analyzed DNA methylation patterns in colorectal adenomas and identified three biologically defined subclasses that describe different intestinal crypt differentiation stages. Importantly, colorectal carcinomas could be classified into the same methylation sub-types, reflecting their shared cell types of origin with adenomas. Further data analysis also revealed significantly reduced overall survival for one of the subtypes. Our results provide a concept for understanding the methylation patterns observed in colorectal cancer and provide opportunities for tumor subclassification and patient stratification.

引用

页码：3407 / 3418

页数：12

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