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

Antonio Fadda, Davide Gentilini, Loredana Moi, Ludovic Barault, Vera Piera Leoni, Pia Sulas, Luigi Zorcolo, Angelo Restivo, Francesco Cabras, Federica Fortunato, Cesare Zavattari, Liliana Varesco, Viviana Gismondi, Maria Rosaria De Miglio, Antonio Mario Scanu, Federica Colombi, Pasquale Lombardi, Ivana Sarotto, Eleonora Loi, Francesco Leone & 4 others Silvia Giordano, Federica Di Nicolantonio, Amedeo Columbano, Patrizia Zavattari

Research output: Contribution to journalArticle

Abstract

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.
Original languageItalian
Pages (from-to)907-920
Number of pages14
JournalInternational Journal of Cancer
Volume143
Issue number4
DOIs
Publication statusPublished - Aug 15 2018

Cite this

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

In: International Journal of Cancer, Vol. 143, No. 4, 15.08.2018, p. 907-920.

Research output: Contribution to journalArticle

Fadda, A, Gentilini, D, Moi, L, Barault, L, Leoni, VP, Sulas, P, Zorcolo, L, Restivo, A, Cabras, F, Fortunato, F, Zavattari, C, Varesco, L, Gismondi, V, De Miglio, MR, Scanu, AM, Colombi, F, Lombardi, P, Sarotto, I, Loi, E, Leone, F, Giordano, S, Di Nicolantonio, F, Columbano, A & Zavattari, P 2018, 'Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor', International Journal of Cancer, vol. 143, no. 4, pp. 907-920. https://doi.org/10.1002/ijc.31380
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. / Colorectal cancer early methylation alterations affect the crosstalk between cell and surrounding environment, tracing a biomarker signature specific for this tumor. In: International Journal of Cancer. 2018 ; Vol. 143, No. 4. pp. 907-920.
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AU - Leoni, Vera Piera

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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

N1 - © 2018 UICC.

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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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KW - Colorectal Neoplasms/genetics

KW - Computer Simulation

KW - CpG Islands

KW - DNA Methylation

KW - Down-Regulation

KW - Feces

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Signal Transduction

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