6533b854fe1ef96bd12ae1c4

RESEARCH PRODUCT

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

Massimo NegriniManuela FerracinAnnalisa NicotraMaria Giulia BacaliniCristian BassiElena SaccentiNoemi LaproviteraRosa VisoneSimone Di FrancoPaolo GaragnaniEmanuela ScavoMaria GrzesRenato Mariani-costantiniNicola ValeriSara PagottoDanilo LicastroMaria Luisa ColoritoAngelo VeroneseGiorgio StassiMirco Di MarcoVincenzo De Laurenzi

subject

0301 basic medicineCancer ResearchMicroarrayColorectal cancercolon cancer stem cellsSocio-culturaleBiologyEpigenesis Genetic03 medical and health sciencesMice0302 clinical medicineGeneticsmedicineAnimalsHumansEpigeneticsneoplasmsMSIMSSMicrosatellite instabilityMethylationcolon cancer stem cells DNA methylation MSI MSSDNA Methylationmedicine.diseasedigestive system diseases030104 developmental biologyCpG siteDrug Resistance Neoplasm030220 oncology & carcinogenesisDNA methylationColonic NeoplasmsCancer researchNeoplastic Stem CellsMicrosatelliteHeterograftsCpG IslandsMicrosatellite Instabilitycolon cancer stem cell

description

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.

yearjournalcountryeditionlanguage
2019-01-01Epigenomics
10.2217/epi-2018-0153https://pubmed.ncbi.nlm.nih.gov/31066579