%0 Journal Article %T DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon cancer stem cells. %A Visone R %A Bacalini MG %A Di Franco S %A Ferracin M %A Colorito ML %A Pagotto S %A Laprovitera N %A Licastro D %A Di Marco M %A Scavo E %A Bassi C %A Saccenti E %A Nicotra A %A Grzes M %A Garagnani P %A De Laurenzi V %A Valeri N %A Mariani-Costantini R %A Negrini M %A Stassi G %A Veronese A %J Epigenomics %V 11 %N 6 %D 05 2019 1 %M 31066579 %F 4.357 %R 10.2217/epi-2018-0153 %X 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 immune-compromised 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.