{Reference Type}: Journal Article {Title}: DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon cancer stem cells. {Author}: Visone R;Bacalini MG;Di Franco S;Ferracin M;Colorito ML;Pagotto S;Laprovitera N;Licastro D;Di Marco M;Scavo E;Bassi C;Saccenti E;Nicotra A;Grzes M;Garagnani P;De Laurenzi V;Valeri N;Mariani-Costantini R;Negrini M;Stassi G;Veronese A; {Journal}: Epigenomics {Volume}: 11 {Issue}: 6 {Year}: 05 2019 1 {Factor}: 4.357 {DOI}: 10.2217/epi-2018-0153 {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 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.