DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon cancer stem cells
- Authors: Visone, Rosa; Bacalini, Maria Giulia; Franco, Simone Di; Ferracin, Manuela; Colorito, Maria Luisa; Pagotto, Sara; Laprovitera, Noemi; Licastro, Danilo; Marco, Mirco Di; Scavo, Emanuela; Bassi, Cristian; Saccenti, Elena; Nicotra, Annalisa; Grzes, Maria; Garagnani, Paolo; Laurenzi, Vincenzo De; Valeri, Nicola; Mariani-Costantini, Renato; Negrini, Massimo; Stassi, Giorgio; Veronese, Angelo
- Publication year: 2019
- Type: Articolo in rivista (Articolo in rivista)
- OA Link: http://hdl.handle.net/10447/354243
Abstract
Aim: To investigate the genome-wide methylation of genetically characterized colorectal cancer stem cell (CR-CSC) lines. Materials & methods: Eight CR-CSC lines were isolated from primary colorectal cancer (CRC) tissues, cultured and characterized for aneuploidy, mutational status of CRC-related genes and microsatellite instability (MSI). Genome-wide DNA methylation was assessed by MethylationEPIC microarray. Results: We describe a distinctive methylation pattern that is maintained following in vivo passages in immunecompromised mice. We identified an epigenetic CR-CSC signature associated with MSI. We noticed that the preponderance of the differentially methylated positions do not reside at CpG islands, but spread to shelf and open sea regions. Conclusion: Given that CRCs with MSI-high status have a lower metastatic potential, the identification of a MSI-related methylation signature could provide new insights and possible targets into metastatic CRC.