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Article: MSH2 c.1452-1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Population

TitleMSH2 c.1452-1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Population
Authors
Issue Date2004
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2004, v. 74 n. 5, p. 1035-1042 How to Cite?
AbstractHereditary nonpolyposis colorectal cancer (HNPCC) accounts for ∼2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome. We have previously reported a high incidence of microsatellite instability (MSI) and germline mismatch repair (MMR) gene mutations in young Hong Kong Chinese with CRC. Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2 c.1452-1455delAATG mutation that has not been reported in other ethnic groups. Detailed analysis showed that this specific MSH2 mutation constituted 21% of all germline MMR gene mutations and 36% of all MSH2 germline mutations identified. We designed a specific PCR-based diagnostic test on paraffin-embedded tissues and identified this germline mutation in 2 1.5%) of 138 consecutive patients with early-onset CRC (<46 years of age at diagnosis). Haplotype analysis was performed using 11 microsatellite markers located between D2S391 and D2S123. All 10 families had the same disease haplotype, suggesting a founder effect. These 10 families all originated from the Chinese province of Guangdong, which historically included Hong Kong. It is the most populous of the Chinese provinces, with a population of >93 million. Further analysis suggested that this founder mutation may date back to between 22 and 103 generations ago. The identification of this MSH2 founder mutation has important implications for the design of mutation-detection strategies for the southern Chinese population. Since there were major emigrations from Hong Kong and Guangdong province during the 19th and 20th centuries, this finding is also significant for Chinese communities worldwide.
Persistent Identifierhttp://hdl.handle.net/10722/54179
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TLen_HK
dc.contributor.authorChan, YWen_HK
dc.contributor.authorHo, JWCen_HK
dc.contributor.authorChan, Cen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorChan, Een_HK
dc.contributor.authorLam, PWYen_HK
dc.contributor.authorTse, CWen_HK
dc.contributor.authorLee, KCen_HK
dc.contributor.authorLau, CWen_HK
dc.contributor.authorGwi, Een_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYuen, STen_HK
dc.date.accessioned2009-04-03T07:38:51Z-
dc.date.available2009-04-03T07:38:51Z-
dc.date.issued2004en_HK
dc.identifier.citationAmerican Journal Of Human Genetics, 2004, v. 74 n. 5, p. 1035-1042en_HK
dc.identifier.issn0002-9297en_HK
dc.identifier.urihttp://hdl.handle.net/10722/54179-
dc.description.abstractHereditary nonpolyposis colorectal cancer (HNPCC) accounts for ∼2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome. We have previously reported a high incidence of microsatellite instability (MSI) and germline mismatch repair (MMR) gene mutations in young Hong Kong Chinese with CRC. Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2 c.1452-1455delAATG mutation that has not been reported in other ethnic groups. Detailed analysis showed that this specific MSH2 mutation constituted 21% of all germline MMR gene mutations and 36% of all MSH2 germline mutations identified. We designed a specific PCR-based diagnostic test on paraffin-embedded tissues and identified this germline mutation in 2 1.5%) of 138 consecutive patients with early-onset CRC (<46 years of age at diagnosis). Haplotype analysis was performed using 11 microsatellite markers located between D2S391 and D2S123. All 10 families had the same disease haplotype, suggesting a founder effect. These 10 families all originated from the Chinese province of Guangdong, which historically included Hong Kong. It is the most populous of the Chinese provinces, with a population of >93 million. Further analysis suggested that this founder mutation may date back to between 22 and 103 generations ago. The identification of this MSH2 founder mutation has important implications for the design of mutation-detection strategies for the southern Chinese population. Since there were major emigrations from Hong Kong and Guangdong province during the 19th and 20th centuries, this finding is also significant for Chinese communities worldwide.en_HK
dc.format.extent386412 bytes-
dc.format.extent2834 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypetext/plain-
dc.languageengen_HK
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_HK
dc.relation.ispartofAmerican Journal of Human Geneticsen_HK
dc.rightsAmerican Journal of Human Genetics. Copyright © University of Chicago Press.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshColorectal Neoplasms, Hereditary Nonpolyposis - ethnology - geneticsen_HK
dc.subject.meshDNA-Binding Proteins - geneticsen_HK
dc.subject.meshFounder Effecten_HK
dc.subject.meshGerm-Line Mutationen_HK
dc.subject.meshProto-Oncogene Proteins - geneticsen_HK
dc.titleMSH2 c.1452-1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Populationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0002-9297&volume=74&issue=5&spage=1035&epage=1042&date=2004&atitle=MSH2+c.1452--1455delAATG+Is+a+Founder+Mutation+and+an+Important+Cause+of+Hereditary+Nonpolyposis+Colorectal+Cancer+in+the+Southern+Chinese+Populationen_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.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1086/383591en_HK
dc.identifier.pmid15042510-
dc.identifier.pmcidPMC1181966-
dc.identifier.scopuseid_2-s2.0-2342464930en_HK
dc.identifier.hkuros86140-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2342464930&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume74en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1035en_HK
dc.identifier.epage1042en_HK
dc.identifier.isiWOS:000220926100021-
dc.publisher.placeUnited Statesen_HK

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