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Conference Paper: BRAF and KRAS mutations in mismatch repair deficient colorectal cancer

TitleBRAF and KRAS mutations in mismatch repair deficient colorectal cancer
Authors
Issue Date2004
PublisherAmerican Association for Cancer Research.
Citation
The 95th Annual Meeting of the American Association for Cancer Research (AACR 2004), Orlando, FL, 27-31 March 2004. In Cancer Research, 2004, v. 64 n. 7S, p. 744, abstract no. 3215 How to Cite?
AbstractActivation of the RAS-RAF-MEK-ERK-MAP kinase pathway plays an important role in colorectal carcinogenesis. We have recently reported the occurrence of BRAF mutation in a small proportion of colorectal cancers and adenomas, and in a high proportion of hyperplastic polyps and serrated adenomas (Cancer Res 2002, 62:6451; Cancer Res 2003, 63:4878). Moreover, the incidence of BRAF mutation was reported to be higher in microsatellite unstable (MSI-H) colorectal cancers. In an ongoing study of more than 500 colorectal cancers, we identified 87 MSI-H tumours. Here we studied these 87 MSI-H colorectal cancers for BRAF and KRAS mutations and examined their relationships with the status of mismatch repair proteins expression, age of onset and hMLH1 promoter methylation status. BRAF and KRAS mutations were identified in 10 (11.5%) and 30 (34.5%) cases respectively. Nine out of 10 BRAF mutations were V599E, the previously described hotspot, and none of these was associated with KRAS mutation. BRAF mutation was found mostly in cancers with hMLH1 protein loss (9 out of 47) and rarely in cancers with hMSH2 loss, hMSH6 loss or no protein loss (1 out of 40)(p=0.037). All 10 cases with BRAF mutation were found in patients aged >50 (n=39), and none was found in patients aged below 50 (p=0.006). No such relationship was found for KRAS mutation. Furthermore, amongst cases with hMLH1 protein loss, BRAF mutation was found exclusively in cases with hMLH1 promoter methylation. (p=0.023). The selective association of BRAF mutation with late-onset MSI-H colorectal cancer with hMLH1 promoter methylation, and its previously reported high incidence in hyperplastic polyps and serrated adenomas, suggest that this group of cancer may have evolved from the serrated neoplasia pathway.
Persistent Identifierhttp://hdl.handle.net/10722/104817
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorChan, TLen_HK
dc.contributor.authorWong, CWen_HK
dc.contributor.authorChan, ASWen_HK
dc.contributor.authorGuo, Den_HK
dc.contributor.authorHo, JWCen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorLeung, SYen_HK
dc.date.accessioned2010-09-25T22:08:33Z-
dc.date.available2010-09-25T22:08:33Z-
dc.date.issued2004en_HK
dc.identifier.citationThe 95th Annual Meeting of the American Association for Cancer Research (AACR 2004), Orlando, FL, 27-31 March 2004. In Cancer Research, 2004, v. 64 n. 7S, p. 744, abstract no. 3215-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104817-
dc.description.abstractActivation of the RAS-RAF-MEK-ERK-MAP kinase pathway plays an important role in colorectal carcinogenesis. We have recently reported the occurrence of BRAF mutation in a small proportion of colorectal cancers and adenomas, and in a high proportion of hyperplastic polyps and serrated adenomas (Cancer Res 2002, 62:6451; Cancer Res 2003, 63:4878). Moreover, the incidence of BRAF mutation was reported to be higher in microsatellite unstable (MSI-H) colorectal cancers. In an ongoing study of more than 500 colorectal cancers, we identified 87 MSI-H tumours. Here we studied these 87 MSI-H colorectal cancers for BRAF and KRAS mutations and examined their relationships with the status of mismatch repair proteins expression, age of onset and hMLH1 promoter methylation status. BRAF and KRAS mutations were identified in 10 (11.5%) and 30 (34.5%) cases respectively. Nine out of 10 BRAF mutations were V599E, the previously described hotspot, and none of these was associated with KRAS mutation. BRAF mutation was found mostly in cancers with hMLH1 protein loss (9 out of 47) and rarely in cancers with hMSH2 loss, hMSH6 loss or no protein loss (1 out of 40)(p=0.037). All 10 cases with BRAF mutation were found in patients aged >50 (n=39), and none was found in patients aged below 50 (p=0.006). No such relationship was found for KRAS mutation. Furthermore, amongst cases with hMLH1 protein loss, BRAF mutation was found exclusively in cases with hMLH1 promoter methylation. (p=0.023). The selective association of BRAF mutation with late-onset MSI-H colorectal cancer with hMLH1 promoter methylation, and its previously reported high incidence in hyperplastic polyps and serrated adenomas, suggest that this group of cancer may have evolved from the serrated neoplasia pathway.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_HK
dc.titleBRAF and KRAS mutations in mismatch repair deficient colorectal canceren_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, TL: tlchan@hku.hken_HK
dc.identifier.emailWong, CW: chiwai81@hkucc.hku.hken_HK
dc.identifier.emailChan, ASW: chansw3@hku.hken_HK
dc.identifier.emailHo, JWC: judyho@HKUCC.hku.hken_HK
dc.identifier.emailYuen, ST: styuen@hkucc.hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChan, ASW=rp00288en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.hkuros86152en_HK
dc.identifier.volume64-
dc.identifier.issue7S-
dc.identifier.spage744, abstract no. 3215-
dc.identifier.epage744, abstract no. 3215-

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