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Article: BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas
Title | BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas |
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Authors | |
Issue Date | 2003 |
Publisher | American 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? |
Abstract | Colorectal 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 Identifier | http://hdl.handle.net/10722/88427 |
ISSN | 2023 Impact Factor: 12.5 2023 SCImago Journal Rankings: 3.468 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chan, TL | en_HK |
dc.contributor.author | Zhao, W | en_HK |
dc.contributor.author | Leung, SY | en_HK |
dc.contributor.author | Yuen, ST | en_HK |
dc.date.accessioned | 2010-09-06T09:43:13Z | - |
dc.date.available | 2010-09-06T09:43:13Z | - |
dc.date.issued | 2003 | en_HK |
dc.identifier.citation | Cancer Research, 2003, v. 63 n. 16, p. 4878-4881 | en_HK |
dc.identifier.issn | 0008-5472 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/88427 | - |
dc.description.abstract | Colorectal 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.language | eng | en_HK |
dc.publisher | American Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/ | en_HK |
dc.relation.ispartof | Cancer Research | en_HK |
dc.subject.mesh | Adenoma - genetics | en_HK |
dc.subject.mesh | Colonic Polyps - genetics | en_HK |
dc.subject.mesh | Colorectal Neoplasms - genetics | en_HK |
dc.subject.mesh | Female | en_HK |
dc.subject.mesh | Genes, ras | en_HK |
dc.subject.mesh | Humans | en_HK |
dc.subject.mesh | Hyperplasia | en_HK |
dc.subject.mesh | Male | en_HK |
dc.subject.mesh | Mutation | en_HK |
dc.subject.mesh | Oncogene Proteins - genetics | en_HK |
dc.subject.mesh | Proto-Oncogene Proteins B-raf | en_HK |
dc.title | BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://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+adenomas | en_HK |
dc.identifier.email | Chan, TL:tlchan@hku.hk | en_HK |
dc.identifier.email | Leung, SY:suetyi@hkucc.hku.hk | en_HK |
dc.identifier.authority | Chan, TL=rp00418 | en_HK |
dc.identifier.authority | Leung, SY=rp00359 | en_HK |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.pmid | 12941809 | - |
dc.identifier.scopus | eid_2-s2.0-0042941629 | en_HK |
dc.identifier.hkuros | 86083 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0042941629&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 63 | en_HK |
dc.identifier.issue | 16 | en_HK |
dc.identifier.spage | 4878 | en_HK |
dc.identifier.epage | 4881 | en_HK |
dc.identifier.isi | WOS:000184948400021 | - |
dc.publisher.place | United States | en_HK |
dc.identifier.issnl | 0008-5472 | - |