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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Felix Bormann - , Universität Heidelberg (Autor:in)
  • Manuel Rodríguez-Paredes - , Universität Heidelberg (Autor:in)
  • Felix Lasitschka - , Universität Heidelberg (Autor:in)
  • Dominic Edelmann - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Tanja Musch - , Universität Heidelberg (Autor:in)
  • Axel Benner - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Yehudit Bergman - , Hebrew University of Jerusalem (Autor:in)
  • Sebastian M. Dieter - , Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Claudia R. Ball - , Nationales Centrum für Tumorerkrankungen Dresden, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Hanno Glimm - , Nationales Centrum für Tumorerkrankungen Dresden, Deutsches Konsortium für Translationale Krebsforschung (Partner: DKTK, DKFZ), Universitätsklinikum Carl Gustav Carus Dresden, Deutsches Krebsforschungszentrum (DKFZ) (Autor:in)
  • Heinz G. Linhart - , Universität Heidelberg, Asklepios Klinik Lindau, Universitätsklinikum Freiburg (Autor:in)
  • Frank Lyko - , Universität Heidelberg (Autor:in)

Abstract

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. Using DNA methylation profiling, Bormann et al. identify three DNA methylation signatures that are conserved between normal crypt sections, colorectal adenomas, and colorectal carcinomas. This suggests that cell-of-origin DNA methylation signatures are stably maintained during colorectal carcinogenesis and provides a framework for the subclassification of colorectal cancer.

Details

OriginalspracheEnglisch
Seiten (von - bis)3407-3418
Seitenumfang12
FachzeitschriftCell reports
Jahrgang23
Ausgabenummer11
PublikationsstatusVeröffentlicht - 12 Juni 2018
Peer-Review-StatusJa

Externe IDs

PubMed 29898408

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • cell-of-origin, colorectal adenoma, colorectal carcinoma, DNA methylation, epigenomics