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Article: Microsatellite instability and novel mismatch repair gene mutations in northern Chinese population with hereditary non-polyposis colorectal cancer.

TitleMicrosatellite instability and novel mismatch repair gene mutations in northern Chinese population with hereditary non-polyposis colorectal cancer.
Authors
Issue Date2006
PublisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journal.asp?ref=1443-9611&site=1
Citation
Chinese Journal Of Digestive Diseases, 2006, v. 7 n. 4, p. 197-205 How to Cite?
AbstractOBJECTIVE: Hereditary non-polyposis colorectal cancer (HNPCC) syndrome is the most common cause of hereditary colorectal cancer with an early age of onset. Microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found in the majority of HNPCC families and provide an opportunity for genetic diagnosis and prophylactic screening. The MMR gene mutation spectrum may vary across different populations and be influenced by founder mutations that prevail in specific ethnic groups. China is a big and ancient nation with enormous genetic diversity, which is especially notable between the northern and southern Chinese populations. A MMR gene mutation database for the southern Chinese population based in Hong Kong has been previously established. This study compares the MMR gene mutation spectrum and the MSI of HNPCC between the northern and southern Chinese populations. METHODS: Twenty-five HNPCC families from northern China were systematically analyzed. The MSI analysis was performed using five loci in the USA National Cancer Institute (NCI) panel (D2S123, D5S346, BAT-25, BAT-26 and BAT-40) by PCR from the tumor and normal tissue. MSH2, MSH6 and MLH1 were performed using immunohistochemical staining. Two founder mutations of MSH2 and MLH1 were examined by PCR base analyses using primers flanking the two deletion sites (c.1452_1455delAATG in MSH2 and 1.8 kb deletion involving exon 11 of MLH1). RESULTS: Of the 25 families collected, 19 met Bethesda guideline (BG) 1 and six met BG3. Twenty-two (15.7%) were extra-colonic cancers with gastric cancer (in seven patients) being the most common cancer type. Of the 25 tumors analyzed, 21 (84%) were high level microsatellite instability (MSI-H) and four (16%) were microsatellite stable (MSS). Eighteen (86%) of the 21 MSI-H tumors showed loss of either the MLH1 or the MSH2 protein. Three MSI-H tumors and all four MSS tumors showed no loss of expression of the three MMR proteins. Out of the 21 patients with MSI-H tumors, 12 (57%) showed pathogenic germline mutations in either MLH1 (n = 8) or MSH2 (n = 4). Overall, three novel mutations (in patients H22, H17 and H29) have been identified. One of them, c.503_4insA, caused a frameshift mutation in the MLH1 gene. The other two were found in the MSH2 gene, including a frameshift (c.899_890insAT) and a splice junction (IVS7-1G-->A, SA of Exon 8) mutation. CONCLUSIONS: The results suggest a distinctly different mutation spectrum of MMR genes between northern and southern Chinese populations and call for a systematic, nationwide study to facilitate the design of a MMR gene mutation detection strategy tailored for individual populations in China.
Persistent Identifierhttp://hdl.handle.net/10722/148499
ISSN

 

DC FieldValueLanguage
dc.contributor.authorSheng, JQen_US
dc.contributor.authorChan, TLen_US
dc.contributor.authorChan, YWen_US
dc.contributor.authorHuang, JSen_US
dc.contributor.authorChen, JGen_US
dc.contributor.authorZhang, MZen_US
dc.contributor.authorGuo, XLen_US
dc.contributor.authorMu, Hen_US
dc.contributor.authorChan, ASen_US
dc.contributor.authorLi, SRen_US
dc.contributor.authorYuen, STen_US
dc.contributor.authorLeung, SYen_US
dc.date.accessioned2012-05-29T06:13:20Z-
dc.date.available2012-05-29T06:13:20Z-
dc.date.issued2006en_US
dc.identifier.citationChinese Journal Of Digestive Diseases, 2006, v. 7 n. 4, p. 197-205en_US
dc.identifier.issn1443-9611en_US
dc.identifier.urihttp://hdl.handle.net/10722/148499-
dc.description.abstractOBJECTIVE: Hereditary non-polyposis colorectal cancer (HNPCC) syndrome is the most common cause of hereditary colorectal cancer with an early age of onset. Microsatellite instability (MSI) and germline mutation in one of the DNA mismatch repair (MMR) genes are found in the majority of HNPCC families and provide an opportunity for genetic diagnosis and prophylactic screening. The MMR gene mutation spectrum may vary across different populations and be influenced by founder mutations that prevail in specific ethnic groups. China is a big and ancient nation with enormous genetic diversity, which is especially notable between the northern and southern Chinese populations. A MMR gene mutation database for the southern Chinese population based in Hong Kong has been previously established. This study compares the MMR gene mutation spectrum and the MSI of HNPCC between the northern and southern Chinese populations. METHODS: Twenty-five HNPCC families from northern China were systematically analyzed. The MSI analysis was performed using five loci in the USA National Cancer Institute (NCI) panel (D2S123, D5S346, BAT-25, BAT-26 and BAT-40) by PCR from the tumor and normal tissue. MSH2, MSH6 and MLH1 were performed using immunohistochemical staining. Two founder mutations of MSH2 and MLH1 were examined by PCR base analyses using primers flanking the two deletion sites (c.1452_1455delAATG in MSH2 and 1.8 kb deletion involving exon 11 of MLH1). RESULTS: Of the 25 families collected, 19 met Bethesda guideline (BG) 1 and six met BG3. Twenty-two (15.7%) were extra-colonic cancers with gastric cancer (in seven patients) being the most common cancer type. Of the 25 tumors analyzed, 21 (84%) were high level microsatellite instability (MSI-H) and four (16%) were microsatellite stable (MSS). Eighteen (86%) of the 21 MSI-H tumors showed loss of either the MLH1 or the MSH2 protein. Three MSI-H tumors and all four MSS tumors showed no loss of expression of the three MMR proteins. Out of the 21 patients with MSI-H tumors, 12 (57%) showed pathogenic germline mutations in either MLH1 (n = 8) or MSH2 (n = 4). Overall, three novel mutations (in patients H22, H17 and H29) have been identified. One of them, c.503_4insA, caused a frameshift mutation in the MLH1 gene. The other two were found in the MSH2 gene, including a frameshift (c.899_890insAT) and a splice junction (IVS7-1G-->A, SA of Exon 8) mutation. CONCLUSIONS: The results suggest a distinctly different mutation spectrum of MMR genes between northern and southern Chinese populations and call for a systematic, nationwide study to facilitate the design of a MMR gene mutation detection strategy tailored for individual populations in China.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journal.asp?ref=1443-9611&site=1en_US
dc.relation.ispartofChinese journal of digestive diseasesen_US
dc.subject.meshAdaptor Proteins, Signal Transducingen_US
dc.subject.meshAdulten_US
dc.subject.meshBase Pair Mismatchen_US
dc.subject.meshCarrier Proteins - Geneticsen_US
dc.subject.meshChinaen_US
dc.subject.meshColorectal Neoplasms, Hereditary Nonpolyposis - Geneticsen_US
dc.subject.meshDna Mismatch Repairen_US
dc.subject.meshDna-Binding Proteins - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshFrameshift Mutationen_US
dc.subject.meshGerm-Line Mutationen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosatellite Instabilityen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMuts Homolog 2 Protein - Geneticsen_US
dc.subject.meshNuclear Proteins - Geneticsen_US
dc.titleMicrosatellite instability and novel mismatch repair gene mutations in northern Chinese population with hereditary non-polyposis colorectal cancer.en_US
dc.typeArticleen_US
dc.identifier.emailChan, TL:tlchan@hku.hken_US
dc.identifier.emailLeung, SY:suetyi@hkucc.hku.hken_US
dc.identifier.authorityChan, TL=rp00418en_US
dc.identifier.authorityLeung, SY=rp00359en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1443-9573.2006.00269.xen_US
dc.identifier.pmid17054581-
dc.identifier.scopuseid_2-s2.0-33846447858en_US
dc.identifier.hkuros126272en_US
dc.identifier.volume7en_US
dc.identifier.issue4en_US
dc.identifier.spage197en_US
dc.identifier.epage205en_US
dc.publisher.placeAustraliaen_US
dc.identifier.citeulike897951-

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