Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor

• Published in: International journal of cancer Vol. 143; no. 4; pp. 907 - 920
• Main Authors: Fadda, Antonio, Gentilini, Davide, Moi, Loredana, Barault, Ludovic, Leoni, Vera Piera, Sulas, Pia, Zorcolo, Luigi, Restivo, Angelo, Cabras, Francesco, Fortunato, Federica, Zavattari, Cesare, Varesco, Liliana, Gismondi, Viviana, De Miglio, Maria Rosaria, Scanu, Antonio Mario, Colombi, Federica, Lombardi, Pasquale, Sarotto, Ivana, Loi, Eleonora, Leone, Francesco, Giordano, Silvia, Di Nicolantonio, Federica, Columbano, Amedeo, Zavattari, Patrizia
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.08.2018
• Subjects: Biomarkers; Cancer; Colon cancer; Colorectal cancer; Colorectal carcinoma; CpG islands; DNA methylation; Gene expression; Medical research; Mucosa; Tumors
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.31380

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. What's new? Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while genetic alterations are already used as prognostic and predictive biomarkers, epigenetic alterations are less well characterized. Here, the authors identified and validated a panel of 74 altered CpG islands able to discriminate CRCs and adenomas from peritumoral and normal mucosa with very high specificity and sensitivity. Three selected markers were tested and detected through non‐invasive techniques, both in circulating tumor DNA and in stool DNA. The earliest methylation alterations affected genes coding for proteins involved in the crosstalk between tumor cells and their surrounding environment.