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Article: A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: A founder mutation in the Chinese population

TitleA novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: A founder mutation in the Chinese population
Authors
KeywordsAlternative splicing
Germline mutation
hMLH1
HNPCC syndrome
Intragenic deletion
Issue Date2001
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2001, v. 20 n. 23, p. 2976-2981 How to Cite?
AbstractWe have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It is well known that alternative splicing is common in hMLH1, which complicates RNA based mutation detection methods. In contrast, large deletions in hMLH1, commonly observed in some ethnic groups, tend to escape detection by exon-by-exon direct DNA sequencing. Here we report the detection of a novel germline 1.8 kb deletion involving exon 11 of hMLH1 in a local hereditary non-polyposis colorectal cancer family. This mutation generates a mRNA transcript with deletion of exons 10-11, which is indistinguishable from one of the most common and predominant hMLH1 splice variants. A diagnostic test based on PCR of the breakpoint region led to the identification of an additional young colorectal cancer patient with this mutation. Haplotype analysis suggests that they may share a common ancestral mutation. Our results caution investigators in the interpretation of alternative splicing and have important implications for the design of hMLH1 mutation detection strategy in the Chinese population.
Persistent Identifierhttp://hdl.handle.net/10722/148266
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TLen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorHo, JWCen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorKwan, Ken_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorLam, PWYen_HK
dc.contributor.authorTse, CWen_HK
dc.contributor.authorLeung, SYen_HK
dc.date.accessioned2012-05-29T06:11:53Z-
dc.date.available2012-05-29T06:11:53Z-
dc.date.issued2001en_HK
dc.identifier.citationOncogene, 2001, v. 20 n. 23, p. 2976-2981en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148266-
dc.description.abstractWe have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It is well known that alternative splicing is common in hMLH1, which complicates RNA based mutation detection methods. In contrast, large deletions in hMLH1, commonly observed in some ethnic groups, tend to escape detection by exon-by-exon direct DNA sequencing. Here we report the detection of a novel germline 1.8 kb deletion involving exon 11 of hMLH1 in a local hereditary non-polyposis colorectal cancer family. This mutation generates a mRNA transcript with deletion of exons 10-11, which is indistinguishable from one of the most common and predominant hMLH1 splice variants. A diagnostic test based on PCR of the breakpoint region led to the identification of an additional young colorectal cancer patient with this mutation. Haplotype analysis suggests that they may share a common ancestral mutation. Our results caution investigators in the interpretation of alternative splicing and have important implications for the design of hMLH1 mutation detection strategy in the Chinese population.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectAlternative splicingen_HK
dc.subjectGermline mutationen_HK
dc.subjecthMLH1en_HK
dc.subjectHNPCC syndromeen_HK
dc.subjectIntragenic deletionen_HK
dc.subject.meshAdaptor Proteins, Signal Transducingen_US
dc.subject.meshAdulten_US
dc.subject.meshAlternative Splicingen_US
dc.subject.meshCarrier Proteinsen_US
dc.subject.meshChinaen_US
dc.subject.meshColorectal Neoplasms - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshFounder Effecten_US
dc.subject.meshGerm-Line Mutationen_US
dc.subject.meshHaplotypes - Geneticsen_US
dc.subject.meshHong Kongen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosatellite Repeatsen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeoplasm Proteins - Geneticsen_US
dc.subject.meshNuclear Proteinsen_US
dc.subject.meshPedigreeen_US
dc.subject.meshPolymerase Chain Reaction - Methodsen_US
dc.subject.meshSequence Deletionen_US
dc.titleA novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: A founder mutation in the Chinese populationen_HK
dc.typeArticleen_HK
dc.identifier.emailChan, TL: tlchan@hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hku.hken_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/sj.onc.1204376en_HK
dc.identifier.pmid11420710-
dc.identifier.scopuseid_2-s2.0-0035942495en_HK
dc.identifier.hkuros57257en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035942495&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume20en_HK
dc.identifier.issue23en_HK
dc.identifier.spage2976en_HK
dc.identifier.epage2981en_HK
dc.identifier.isiWOS:000168901800013-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, TL=7402687537en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridHo, JWC=25925854200en_HK
dc.identifier.scopusauthoridChan, ASY=7403168075en_HK
dc.identifier.scopusauthoridKwan, K=7006405778en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridLam, PWY=7202365931en_HK
dc.identifier.scopusauthoridTse, CW=36958765600en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK

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