Journal
EPIGENOMICS
Volume 11, Issue 6, Pages 587-604Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2018-0153
Keywords
colon cancer stem cells; DNA methylation; MSI; MSS
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Funding
- Italian Ministry of Health funds [GR-2011-02350699]
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 16746, 5 x 1000 9979]
- Umberto Veronesi foundation
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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 Methylation EPIC 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.
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