<i>MUC5</i><scp><i>AC</i></scp> hypomethylation is a predictor of microsatellite instability independently of clinical factors associated with colorectal cancer
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- Florence Renaud
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Audrey Vincent
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Christophe Mariette
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Michel Crépin
- Department of Molecular Oncology and Genetics Biochemistry and Molecular Biology Institute, Biology Pathology Center, Lille University Hospital Lille France
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- Laurence Stechly
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Stéphanie Truant
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Marie‐Christine Copin
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Nicole Porchet
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Emmanuelle Leteurtre
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Isabelle Van Seuningen
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
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- Marie‐Pierre Buisine
- Inserm, UMR837, Team 5 “Mucins, Epithelial Differentiation and Carcinogenesis,” Jean‐Pierre Aubert Research Center Lille France
説明
<jats:p>Colorectal cancers (CRC) with microsatellite instability (MSI) display unique clinicopathologic features including a mucinous pattern with frequent expression of the secreted mucins MUC2 and MUC5AC. The mechanisms responsible for this altered pattern of expression remain largely unknown. We quantified DNA methylation of mucin genes (<jats:italic>MUC2</jats:italic>, <jats:italic>MUC5AC</jats:italic>, <jats:italic>MUC4</jats:italic>) in colonic cancers and examined the association with clinicopathological characteristics and molecular (MSI, <jats:italic>KRAS</jats:italic>, <jats:italic>BRAF,</jats:italic> and <jats:italic>TP53</jats:italic> mutations) features. A control cohort was used for validation. We detected frequent hypomethylation of <jats:italic>MUC2</jats:italic> and <jats:italic>MUC5AC</jats:italic> in CRC. <jats:italic>MUC2</jats:italic> and <jats:italic>MUC5AC</jats:italic> hypomethylation was associated with MUC2 and MUC5AC protein expression (<jats:italic>p</jats:italic> = 0.004 and <jats:italic>p</jats:italic> < 0.001, respectively), poor differentiation (<jats:italic>p</jats:italic> = 0.001 and <jats:italic>p</jats:italic> = 0.007, respectively) and MSI status (<jats:italic>p</jats:italic> < 0.01 and <jats:italic>p</jats:italic> < 0.001, respectively). Interestingly, <jats:italic>MUC5AC</jats:italic> hypomethylation was specific to MSI cancers. Moreover, it was significantly associated with <jats:italic>BRAF</jats:italic> mutation and CpG island methylator phenotype (<jats:italic>p</jats:italic> < 0.001 and <jats:italic>p</jats:italic> < 0.001, respectively). All these results were confirmed in the control cohort. In the multivariate analysis, <jats:italic>MUC5AC</jats:italic> hypomethylation was a highly predictive biomarker for MSI cancers. <jats:italic>MUC5AC</jats:italic> demethylation appears to be a hallmark of MSI in CRC. Determination of <jats:italic>MUC5AC</jats:italic> methylation status may be useful for understanding and predicting the natural history of CRC.</jats:p>
収録刊行物
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- International Journal of Cancer
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International Journal of Cancer 136 (12), 2811-2821, 2014-12-04
Wiley