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Article: Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

TitleHeritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer
Authors
Issue Date2006
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
Citation
Nature Genetics, 2006, v. 38 n. 10, p. 1178-1183 How to Cite?
AbstractEpimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy. © 2006 Nature Publishing Group.
Persistent Identifierhttp://hdl.handle.net/10722/88824
ISSN
2015 Impact Factor: 31.616
2015 SCImago Journal Rankings: 23.762
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TLen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorKong, CKen_HK
dc.contributor.authorChan, YWen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorNg, WFen_HK
dc.contributor.authorTsui, WYen_HK
dc.contributor.authorLo, MWSen_HK
dc.contributor.authorTam, WYen_HK
dc.contributor.authorLi, VSWen_HK
dc.contributor.authorLeung, SYen_HK
dc.date.accessioned2010-09-06T09:48:28Z-
dc.date.available2010-09-06T09:48:28Z-
dc.date.issued2006en_HK
dc.identifier.citationNature Genetics, 2006, v. 38 n. 10, p. 1178-1183en_HK
dc.identifier.issn1061-4036en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88824-
dc.description.abstractEpimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy. © 2006 Nature Publishing Group.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.comen_HK
dc.relation.ispartofNature Geneticsen_HK
dc.subject.meshAdulten_HK
dc.subject.meshColorectal Neoplasms, Hereditary Nonpolyposis - genetics - pathologyen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGerm-Line Mutationen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMutS Homolog 2 Protein - geneticsen_HK
dc.subject.meshPedigreeen_HK
dc.titleHeritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1061-4036&volume=38&issue=10&spage=1178&epage=83&date=2006&atitle=Heritable+germline+epimutation+of+MSH2+in+a+family+with+hereditary+nonpolyposis+colorectal+canceren_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_subscribed_fulltext-
dc.identifier.doi10.1038/ng1866en_HK
dc.identifier.pmid16951683-
dc.identifier.scopuseid_2-s2.0-33749122904en_HK
dc.identifier.hkuros122855en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33749122904&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume38en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1178en_HK
dc.identifier.epage1183en_HK
dc.identifier.eissn1546-1718-
dc.identifier.isiWOS:000241251100018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001066011-
dc.identifier.citeulike876188-

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