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Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients.
Rawson, J B; Mrkonjic, M; Daftary, D; Dicks, E; Buchanan, D D; Younghusband, H B; Parfrey, P S; Young, J P; Pollett, A; Green, R C; Gallinger, S; McLaughlin, J R; Knight, J A; Bapat, B.
Afiliación
  • Rawson JB; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A1.
Br J Cancer ; 104(12): 1906-12, 2011 Jun 07.
Article en En | MEDLINE | ID: mdl-21587258
BACKGROUND: In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs. METHODS: Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival. RESULTS: In Ontario, Wnt5a methylation was strongly associated with MSI tumours after adjustment for age, sex, and tumour location (odds ratio (OR)=4.2, 95% confidence interval (CI)=2.4-7.4, P<10(-6)) and with BRAF V600E mutation, a marker of CIMP (OR=12.3, 95% CI=6.9-21.7, P<10(-17)), but was not associated with patient survival. Concordant results were obtained in Newfoundland. CONCLUSION: Methylation of Wnt5a is associated with distinct tumour subtypes, strengthening the evidence of an epigenetic-mediated Wnt bias in CRC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas Proto-Oncogénicas / Regiones Promotoras Genéticas / Metilación de ADN / Proteínas Proto-Oncogénicas B-raf / Proteínas Wnt / Inestabilidad de Microsatélites / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Cancer Año: 2011 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Proteínas Proto-Oncogénicas / Regiones Promotoras Genéticas / Metilación de ADN / Proteínas Proto-Oncogénicas B-raf / Proteínas Wnt / Inestabilidad de Microsatélites / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Cancer Año: 2011 Tipo del documento: Article Pais de publicación: Reino Unido