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Article: CpG island methylation in aberrant crypt foci of the colorectum

TitleCpG island methylation in aberrant crypt foci of the colorectum
Authors
Issue Date2002
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
Citation
American Journal of Pathology, 2002, v. 160 n. 5, p. 1823-30 How to Cite?
AbstractAberrant crypt foci (ACF) are postulated to be the earliest precursor lesion in colorectal carcinogenesis, and CpG island methylation has been described as an important molecular pathway. We therefore studied methylation in ACF from patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer. We assessed methylation status of the p16 tumor suppressor gene, MINT1 (methylated in tumor 1), MINT2, MINT31, O(6)-methylguanine-DNA methyltransferase gene, and hMLH1 mismatch repair gene. We compared methylation to ACF histopathology, K-ras proto-oncogene mutation, loss of heterozygosity at chromosome 1p, and microsatellite instability. Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation was the only molecular abnormality identified in 16% (10 of 61) of ACF. Our findings suggest that methylation in ACF is an early event in the pathogenesis of a subset of colorectal carcinomas, and that ACF from FAP patients and patients with sporadic colorectal cancer have distinct epigenetic changes that reflect differences in molecular pathogenesis.
Persistent Identifierhttp://hdl.handle.net/10722/49125
ISSN
2023 Impact Factor: 4.7
2023 SCImago Journal Rankings: 1.647
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, AOOen_HK
dc.contributor.authorBroaddus, RRen_HK
dc.contributor.authorHoulihan, PSen_HK
dc.contributor.authorIssa, JPJen_HK
dc.contributor.authorHamilton, SRen_HK
dc.contributor.authorRashid, Aen_HK
dc.date.accessioned2008-06-12T06:34:57Z-
dc.date.available2008-06-12T06:34:57Z-
dc.date.issued2002en_HK
dc.identifier.citationAmerican Journal of Pathology, 2002, v. 160 n. 5, p. 1823-30en_HK
dc.identifier.issn0002-9440en_HK
dc.identifier.urihttp://hdl.handle.net/10722/49125-
dc.description.abstractAberrant crypt foci (ACF) are postulated to be the earliest precursor lesion in colorectal carcinogenesis, and CpG island methylation has been described as an important molecular pathway. We therefore studied methylation in ACF from patients with familial adenomatous polyposis (FAP) or sporadic colorectal cancer. We assessed methylation status of the p16 tumor suppressor gene, MINT1 (methylated in tumor 1), MINT2, MINT31, O(6)-methylguanine-DNA methyltransferase gene, and hMLH1 mismatch repair gene. We compared methylation to ACF histopathology, K-ras proto-oncogene mutation, loss of heterozygosity at chromosome 1p, and microsatellite instability. Methylation was present in 34% (21 of 61) of ACF, including both FAP and sporadic types, but was more frequent in sporadic ACF [53% (18 of 34) versus 11% (3 of 27), P = 0.002], especially dysplastic sporadic ACF [75% (3 of 4) versus 8% (2 of 24), P = 0.004]. MINT31 was more frequently methylated in heteroplastic ACF than dysplastic ACF [35% (11 of 31) versus 7% (2 of 30), P = 0.01]. Strong associations of ACF methylation with K-ras mutation (P = 0.007) and with loss of chromosome 1p (P = 0.04) were observed, but methylation was the only molecular abnormality identified in 16% (10 of 61) of ACF. Our findings suggest that methylation in ACF is an early event in the pathogenesis of a subset of colorectal carcinomas, and that ACF from FAP patients and patients with sporadic colorectal cancer have distinct epigenetic changes that reflect differences in molecular pathogenesis.en_HK
dc.format.extent388 bytes-
dc.format.mimetypetext/html-
dc.languageengen_HK
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.orgen_HK
dc.subject.meshColon - metabolism - pathologyen_HK
dc.subject.meshColorectal Neoplasms - genetics - pathologyen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshCpG Islands - geneticsen_HK
dc.subject.meshPrecancerous Conditions - genetics - pathologyen_HK
dc.titleCpG island methylation in aberrant crypt foci of the colorectumen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9440&volume=160&issue=5&spage=1823&epage=30&date=2002&atitle=CpG+island+methylation+in+aberrant+crypt+foci+of+the+colorectumen_HK
dc.identifier.emailChan, AOO: aoochan@HKUCC.hku.hken_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1016/S0002-9440(10)61128-5-
dc.identifier.pmid12000733-
dc.identifier.pmcidPMC1850869en_HK
dc.identifier.scopuseid_2-s2.0-0036098559-
dc.identifier.hkuros80839-
dc.identifier.isiWOS:000175468200030-
dc.identifier.issnl0002-9440-

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