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Cell-of-origin DNA methylation signatures are maintained during colorectal carcinogenesis

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...

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Main Authors: Bormann, Felix (Author) , Rodríguez Paredes, Manuel (Author) , Lasitschka, Felix (Author) , Edelmann, Dominic (Author) , Musch, Tanja (Author) , Benner, Axel (Author) , Bergman, Yehudit (Author) , Dieter, Sebastian M. (Author) , Ball, Claudia R. (Author) , Glimm, Hanno (Author) , Linhart, Heinz G. (Author) , Lyko, Frank (Author)
Format: Article (Journal)
Language:English
Published: June 12, 2018
In: Cell reports
Year: 2018, Volume: 23, Issue: 11, Pages: 3407-3418
ISSN:2211-1247
DOI:10.1016/j.celrep.2018.05.045
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2018.05.045
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124718307915
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Author Notes:Felix Bormann, Manuel Rodríguez-Paredes, Felix Lasitschka, Dominic Edelmann, Tanja Musch, Axel Benner, Yehudit Bergman, Sebastian M. Dieter, Claudia R. Ball, Hanno Glimm, Heinz G. Linhart, and Frank Lyko
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Summary: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.
Item Description:Gesehen am 31.03.2020
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2018.05.045

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