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Article: BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas

TitleBRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas
Authors
Issue Date2003
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2003, v. 63 n. 16, p. 4878-4881 How to Cite?
AbstractColorectal cancer is believed to progress through an adenoma-carcinoma sequence. However, recent evidence increasingly supports the existence of an alternative route for colorectal carcinogenesis through serrated polyps, a group that encompasses a morphological spectrum, including hyperplastic polyp (HP), admixed hyperplastic polyp/adenoma (HP/AD), and serrated adenoma (SA; the latter two manifest epithelial dysplasia). We have studied a large series of serrated polyps for BRAF and KRAS mutations. BRAF mutations were detected in 18 of 50 (36%) HPs, 2 of 10 (20%) HP/ADs, and 9 of 9 (100%) SAs. Twenty-six of 29 mutations caused amino acid substitutions at valine 599, the known hotspot. KRAS mutations were detected in 9 of 50 (18%) HPs, 6 of 10 (60%) HP/ADs, and 0 of 9 (0%) SAs. BRAF and KRAS mutations are mutually exclusive (P = 0.001). The associations of BRAF mutations with SAs (P < 0.001) and KRAS mutations with HP/ADs (P = 0.005) are statistically significant. A majority (90%) of the serrated polyps showing dysplasia had mutations in either BRAF or KRAS, significantly different from those without dysplasia (54%; P = 0.014). Our data highlight the important role of activation of the RAS-RAF-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase-mitogen-activated protein kinase pathway in the initiation and progression of serrated neoplasms. Acquisition of a BRAF mutation appears to be associated with the progression of HP to SA, whereas progression to HP/AD is predominantly associated with acquisition of a KRAS mutation. The high incidence of BRAF mutations in HPs and SAs is consistent with the notion that the group of colorectal cancers carrying BRAF mutations may harbor most that have progressed through the HP-SA-carcinoma pathway.
Persistent Identifierhttp://hdl.handle.net/10722/88427
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TLen_HK
dc.contributor.authorZhao, Wen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYuen, STen_HK
dc.date.accessioned2010-09-06T09:43:13Z-
dc.date.available2010-09-06T09:43:13Z-
dc.date.issued2003en_HK
dc.identifier.citationCancer Research, 2003, v. 63 n. 16, p. 4878-4881en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88427-
dc.description.abstractColorectal cancer is believed to progress through an adenoma-carcinoma sequence. However, recent evidence increasingly supports the existence of an alternative route for colorectal carcinogenesis through serrated polyps, a group that encompasses a morphological spectrum, including hyperplastic polyp (HP), admixed hyperplastic polyp/adenoma (HP/AD), and serrated adenoma (SA; the latter two manifest epithelial dysplasia). We have studied a large series of serrated polyps for BRAF and KRAS mutations. BRAF mutations were detected in 18 of 50 (36%) HPs, 2 of 10 (20%) HP/ADs, and 9 of 9 (100%) SAs. Twenty-six of 29 mutations caused amino acid substitutions at valine 599, the known hotspot. KRAS mutations were detected in 9 of 50 (18%) HPs, 6 of 10 (60%) HP/ADs, and 0 of 9 (0%) SAs. BRAF and KRAS mutations are mutually exclusive (P = 0.001). The associations of BRAF mutations with SAs (P < 0.001) and KRAS mutations with HP/ADs (P = 0.005) are statistically significant. A majority (90%) of the serrated polyps showing dysplasia had mutations in either BRAF or KRAS, significantly different from those without dysplasia (54%; P = 0.014). Our data highlight the important role of activation of the RAS-RAF-mitogen-activated protein/extracellular signal-regulated kinase kinase-extracellular signal-regulated kinase-mitogen-activated protein kinase pathway in the initiation and progression of serrated neoplasms. Acquisition of a BRAF mutation appears to be associated with the progression of HP to SA, whereas progression to HP/AD is predominantly associated with acquisition of a KRAS mutation. The high incidence of BRAF mutations in HPs and SAs is consistent with the notion that the group of colorectal cancers carrying BRAF mutations may harbor most that have progressed through the HP-SA-carcinoma pathway.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAdenoma - geneticsen_HK
dc.subject.meshColonic Polyps - geneticsen_HK
dc.subject.meshColorectal Neoplasms - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGenes, rasen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHyperplasiaen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMutationen_HK
dc.subject.meshOncogene Proteins - geneticsen_HK
dc.subject.meshProto-Oncogene Proteins B-rafen_HK
dc.titleBRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomasen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-5472&volume=63&spage=4878&epage=4881&date=2003&atitle=BRAF+and+KRAS+mutations+in+colorectal+hyperplastic+polyps+and+serrated+adenomasen_HK
dc.identifier.emailChan, TL:tlchan@hku.hken_HK
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid12941809-
dc.identifier.scopuseid_2-s2.0-0042941629en_HK
dc.identifier.hkuros86083en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0042941629&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume63en_HK
dc.identifier.issue16en_HK
dc.identifier.spage4878en_HK
dc.identifier.epage4881en_HK
dc.identifier.isiWOS:000184948400021-
dc.publisher.placeUnited Statesen_HK

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