Rosa Visone1,2, Maria Giulia Bacalini3, Simone Di Franco4, Manuela Ferracin5, Maria Luisa Colorito4, Sara Pagotto1,2, Noemi Laprovitera5, Danilo Licastro6, Mirco Di Marco1,2, Emanuela Scavo5, Cristian Bassi7, Elena Saccenti7, Annalisa Nicotra5, Maria Grzes3,8, Paolo Garagnani5, Vincenzo De Laurenzi1,2, Nicola Valeri9, Renato Mariani-Costantini1,2, Massimo Negrini7, Giorgio Stassi5, Angelo Veronese2,10. 1. Department of Medical, Oral & Biotechnological Sciences, G. d'Annunzio University, Chieti-Pescara, Italy. 2. Center of Aging Science & Translational Medicine (CeSI-MeT), G. d'Annunzio University, Chieti, Italy. 3. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italia. 4. Cellular & Molecular Pathophysiology Laboratory, Department of Surgical, Oncological & Stomatological Sciences, University of Palermo, Palermo, Italy. 5. Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. 6. CBM S.c.r.l. Area Science Park, Trieste, Italy. 7. Department of Morphology, Surgery & Experimental Medicine, University of Ferrara, Ferrara, Italy. 8. Department of Molecular Biology, Institute of Genetics & Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland. 9. Division of Molecular Pathology, The Institute of Cancer Research, London, UK. 10. Department of Medicine & Aging Science, G. d'Annunzio University, Chieti-Pescara, Italy.
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.
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.
Entities:
Keywords:
DNA methylation; MSI; MSS; colon cancer stem cells
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