Open AccessCell-of-Origin DNA Methylation Signatures Are Maintained during Colorectal Carcinogenesis
Author(s) -
Felix Bormann,
Manuel RodríguezParedes,
Felix Lasitschka,
Dominic Edelmann,
Tanja Musch,
Axel Benner,
Yehudit Bergman,
Sebastian M. Dieter,
Claudia R. Ball,
Hanno Glimm,
Heinz Linhart,
Frank Lyko
Publication year - 2018
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2018.05.045
Subject(s) - dna methylation , carcinogenesis , methylation , biology , cancer research , colorectal cancer , dna , cell , epigenetics , microbiology and biotechnology , genetics , computational biology , cancer , gene , gene expression
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 subtypes, 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.
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