Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients

被引：33

作者：

Rawson, J. B. ^{[1
,2
]}

Mrkonjic, M. ^{[1
,2
]}

Daftary, D. ^{[3
]}

Dicks, E. ^{[4
]}

Buchanan, D. D. ^{[5
]}

Younghusband, H. B. ^{[4
]}

Parfrey, P. S. ^{[4
]}

Young, J. P. ^{[5
]}

Pollett, A. ^{[6
]}

Green, R. C. ^{[4
]}

Gallinger, S. ^{[1
,2
,3
,7
]}

McLaughlin, J. R. ^{[2
,8
]}

Knight, J. A. ^{[2
,8
]}

Bapat, B. ^{[1
,2
,6
]}

机构：

[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada

[2] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[3] Canc Care Ontario, Ontario Familial Colorectal Canc Registry, Toronto, ON M5G 2L7, Canada

[4] Mem Univ Newfoundland, Fac Med, St John, NF A1C 5S7, Canada

[5] Queensland Inst Med Res, Familial Canc Lab, Herston, Qld 4006, Australia

[6] Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada

[7] Univ Toronto, Dept Surg, Toronto, ON M5S 1A1, Canada

[8] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 2S1, Canada

来源：

BRITISH JOURNAL OF CANCER | 2011年 / 104卷 / 12期

基金：

美国国家卫生研究院; 加拿大健康研究院;

关键词：

colorectal cancer; methylation; Wnt; microsatellite instability; COLON-CANCER; EPIGENETIC CHANGES; TUMOR-SUPPRESSOR; DNA METHYLATION; PROSTATE-CANCER; WNT-5A PROTEIN; EXPRESSION; PATHWAY; NEWFOUNDLAND; CARCINOMAS;

D O I：

10.1038/bjc.2011.165

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. British Journal of Cancer (2011) 104, 1906-1912. doi:10.1038/bjc.2011.165 www.bjcancer.com Published online 17 May 2011 (C) 2011 Cancer Research UK

引用

页码：1906 / 1912

页数：7

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