TY - JOUR
T1 - Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor
AU - Fadda, Antonio
AU - Gentilini, Davide
AU - Moi, Loredana
AU - Barault, Ludovic
AU - Leoni, Vera Piera
AU - Sulas, Pia
AU - Zorcolo, Luigi
AU - Restivo, Angelo
AU - Cabras, Francesco
AU - Fortunato, Federica
AU - Zavattari, Cesare
AU - Varesco, Liliana
AU - Gismondi, Viviana
AU - De Miglio, Maria Rosaria
AU - Scanu, Antonio Mario
AU - Colombi, Federica
AU - Lombardi, Pasquale
AU - Sarotto, Ivana
AU - Loi, Eleonora
AU - Leone, Francesco
AU - Giordano, Silvia
AU - Di Nicolantonio, Federica
AU - Columbano, Amedeo
AU - Zavattari, Patrizia
PY - 2018/8/15
Y1 - 2018/8/15
N2 - Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment. The panel discriminates CRCs and adenomas from peritumoral and normal mucosa with very high specificity (100%) and sensitivity (99.9%). Interestingly, over 70% of the hypermethylated islands resulted in downregulation of gene expression. To establish the possible usefulness of these non-invasive markers for detection of colon cancer, we selected three biomarkers and identified the presence of altered methylation in stool DNA and plasma cell-free circulating DNA from CRC patients.
AB - Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment. The panel discriminates CRCs and adenomas from peritumoral and normal mucosa with very high specificity (100%) and sensitivity (99.9%). Interestingly, over 70% of the hypermethylated islands resulted in downregulation of gene expression. To establish the possible usefulness of these non-invasive markers for detection of colon cancer, we selected three biomarkers and identified the presence of altered methylation in stool DNA and plasma cell-free circulating DNA from CRC patients.
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U2 - 10.1002/ijc.31380
DO - 10.1002/ijc.31380
M3 - Article
AN - SCOPUS:85044850213
VL - 143
SP - 907
EP - 920
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -