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Conference Paper: Elevated copy number and extensive microsatellite instability in mitochondrial genome of human endometrial adenocarcinoma

TitleElevated copy number and extensive microsatellite instability in mitochondrial genome of human endometrial adenocarcinoma
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research.
Citation
The 96th Annual Meeting of the American Association for Cancer Research (AACR), Anaheim, CA., 16-20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 830, abstract no. 3523 How to Cite?
AbstractObjective: Mitochondrial DNA (mtDNA) mutations and genetic instability were frequently detected in human cancers. However, only limited data are available on the levels of mtDNA copy number in cancers. Thus, we investigated the mtDNA copy number and mutations in pure endometrial cancer cells obtained by laser capture microdissection (LCM). Methods: Quantitative analyses of levels of mtDNA copy number by real-time PCR were performed in pure endometrial cancer cells and in pure normal endometrial glandular epithelial cells procured by LCM from 65 cases of primary endometrial adenocarcinomas and 41 cases of normal endometrium tissues. In addition, separated areas on endometrial cancer sections and adjacent areas with normal cells from 18 cases showing mitochondrial microsatellite instability (mtMSI) and 3 mtMSI-negative cases identified in our previous study were also collected. The occurrence of mtMSI and mutations in each particular section were determined by polyacrylamide gel electrophoresis followed by DNA sequencing. Results: About 2 folds increase of mtDNA copy number was found in endometrial adenocarcinoma compared to normal endometrium (ANOVA test, F=11.358, P=0.001, df=1, 104). The analysis also shows that the copy number of mtDNA in the cases which carried the mtMSI at nucleotide position 303 was significantly higher than that of the negative cases (ANOVA test, F=4.194, P=0.048, df=1, 38). In addition, highly heterogeneous sequence alterations in microsatellite regions of mtDNA were observed in different tumor areas from the same sample. A serial number of mutations, which was not detectable from the gross tumor samples, was also detected from a small population of tumor cell isolated by LCM. Interestingly, most mutations were found to be heteroplasmic. Conclusions: Elevated mtDNA copy number was observed in endometrial carcinomas and it may be related to the mtMSI in the D-loop region that controls mtDNA replication. The high frequency of heteroplasmic mtDNA mutations detected in difference patches of tumor cells from same lesion suggests that the occurrence of mtDNA mutations was extensive and might be heavily underestimated in many previous investigations. Thus, functional impact of mtDNA mutation warrants further investigation.
Persistent Identifierhttp://hdl.handle.net/10722/113503
ISSN
2023 Impact Factor: 12.5
2023 SCImago Journal Rankings: 3.468

 

DC FieldValueLanguage
dc.contributor.authorWang, Yen_HK
dc.contributor.authorLiu, VWSen_HK
dc.contributor.authorTsang, PCKen_HK
dc.contributor.authorXue, WCen_HK
dc.contributor.authorCheung, ANYen_HK
dc.contributor.authorNgan, HYSen_HK
dc.date.accessioned2010-09-26T04:18:43Z-
dc.date.available2010-09-26T04:18:43Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 96th Annual Meeting of the American Association for Cancer Research (AACR), Anaheim, CA., 16-20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 830, abstract no. 3523-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/113503-
dc.description.abstractObjective: Mitochondrial DNA (mtDNA) mutations and genetic instability were frequently detected in human cancers. However, only limited data are available on the levels of mtDNA copy number in cancers. Thus, we investigated the mtDNA copy number and mutations in pure endometrial cancer cells obtained by laser capture microdissection (LCM). Methods: Quantitative analyses of levels of mtDNA copy number by real-time PCR were performed in pure endometrial cancer cells and in pure normal endometrial glandular epithelial cells procured by LCM from 65 cases of primary endometrial adenocarcinomas and 41 cases of normal endometrium tissues. In addition, separated areas on endometrial cancer sections and adjacent areas with normal cells from 18 cases showing mitochondrial microsatellite instability (mtMSI) and 3 mtMSI-negative cases identified in our previous study were also collected. The occurrence of mtMSI and mutations in each particular section were determined by polyacrylamide gel electrophoresis followed by DNA sequencing. Results: About 2 folds increase of mtDNA copy number was found in endometrial adenocarcinoma compared to normal endometrium (ANOVA test, F=11.358, P=0.001, df=1, 104). The analysis also shows that the copy number of mtDNA in the cases which carried the mtMSI at nucleotide position 303 was significantly higher than that of the negative cases (ANOVA test, F=4.194, P=0.048, df=1, 38). In addition, highly heterogeneous sequence alterations in microsatellite regions of mtDNA were observed in different tumor areas from the same sample. A serial number of mutations, which was not detectable from the gross tumor samples, was also detected from a small population of tumor cell isolated by LCM. Interestingly, most mutations were found to be heteroplasmic. Conclusions: Elevated mtDNA copy number was observed in endometrial carcinomas and it may be related to the mtMSI in the D-loop region that controls mtDNA replication. The high frequency of heteroplasmic mtDNA mutations detected in difference patches of tumor cells from same lesion suggests that the occurrence of mtDNA mutations was extensive and might be heavily underestimated in many previous investigations. Thus, functional impact of mtDNA mutation warrants further investigation.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_HK
dc.titleElevated copy number and extensive microsatellite instability in mitochondrial genome of human endometrial adenocarcinomaen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLiu, VWS: vwsliu@hkusua.hku.hken_HK
dc.identifier.emailTsang, PCK: pcktsang@HKUCC.hku.hken_HK
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hken_HK
dc.identifier.authorityLiu, VWS=rp00341en_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.hkuros101831en_HK
dc.identifier.volume65-
dc.identifier.issue9 suppl.-
dc.identifier.spage830, abstract no. 3523-
dc.identifier.epage830, abstract no. 3523-
dc.identifier.issnl0008-5472-

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