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DNA methylation of shelf, shore and open sea CpG positions distinguish high microsatellite instability from low or stable microsatellite status colon cancer stem cells

  • Autori: Visone, R.; Bacalini, M.; Franco, S.; Ferracin, M.; Colorito, M.; Pagotto, S.; Laprovitera, N.; Licastro, D.; Marco, M.; Scavo, E.; Bassi, C.; Saccenti, E.; Nicotra, A.; Grzes, M.; Garagnani, P.; Laurenzi, V.; Valeri, N.; Mariani-Costantini, R.; Negrini, M.; Stassi, G.; Veronese, A.
  • Anno di pubblicazione: 2019
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • OA Link:


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.