Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients
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...
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ftumelbourne:oai:jupiter.its.unimelb.edu.au:11343/268848 2024-06-02T08:10:45+00:00 Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients Rawson, JB Mrkonjic, M Daftary, D Dicks, E Buchanan, DD Younghusband, HB Parfrey, PS Young, JP Pollett, A Green, RC Gallinger, S McLaughlin, JR Knight, JA Bapat, B 2011-06-07 http://hdl.handle.net/11343/268848 English eng NATURE PUBLISHING GROUP issn:0007-0920 doi:10.1038/bjc.2011.165 pii: bjc2011165 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. (2011). Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients. BRITISH JOURNAL OF CANCER, 104 (12), pp.1906-1912. https://doi.org/10.1038/bjc.2011.165. 1532-1827 http://hdl.handle.net/11343/268848 CC BY https://creativecommons.org/licenses/by/4.0 Journal Article 2011 ftumelbourne https://doi.org/10.1038/bjc.2011.165 2024-05-06T11:50:00Z 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. Article in Journal/Newspaper Newfoundland The University of Melbourne: Digital Repository Canada British Journal of Cancer 104 12 1906 1912 |
institution |
Open Polar |
collection |
The University of Melbourne: Digital Repository |
op_collection_id |
ftumelbourne |
language |
English |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Rawson, JB Mrkonjic, M Daftary, D Dicks, E Buchanan, DD Younghusband, HB Parfrey, PS Young, JP Pollett, A Green, RC Gallinger, S McLaughlin, JR Knight, JA Bapat, B |
spellingShingle |
Rawson, JB Mrkonjic, M Daftary, D Dicks, E Buchanan, DD Younghusband, HB Parfrey, PS Young, JP Pollett, A Green, RC Gallinger, S McLaughlin, JR Knight, JA Bapat, B Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients |
author_facet |
Rawson, JB Mrkonjic, M Daftary, D Dicks, E Buchanan, DD Younghusband, HB Parfrey, PS Young, JP Pollett, A Green, RC Gallinger, S McLaughlin, JR Knight, JA Bapat, B |
author_sort |
Rawson, JB |
title |
Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients |
title_short |
Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients |
title_full |
Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients |
title_fullStr |
Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients |
title_full_unstemmed |
Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients |
title_sort |
promoter methylation of wnt5a is associated with microsatellite instability and braf v600e mutation in two large populations of colorectal cancer patients |
publisher |
NATURE PUBLISHING GROUP |
publishDate |
2011 |
url |
http://hdl.handle.net/11343/268848 |
geographic |
Canada |
geographic_facet |
Canada |
genre |
Newfoundland |
genre_facet |
Newfoundland |
op_relation |
issn:0007-0920 doi:10.1038/bjc.2011.165 pii: bjc2011165 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. (2011). Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients. BRITISH JOURNAL OF CANCER, 104 (12), pp.1906-1912. https://doi.org/10.1038/bjc.2011.165. 1532-1827 http://hdl.handle.net/11343/268848 |
op_rights |
CC BY https://creativecommons.org/licenses/by/4.0 |
op_doi |
https://doi.org/10.1038/bjc.2011.165 |
container_title |
British Journal of Cancer |
container_volume |
104 |
container_issue |
12 |
container_start_page |
1906 |
op_container_end_page |
1912 |
_version_ |
1800756665734135808 |