Detection of mosaic pattern of mitochondrial DNA alterations in different populations of cells from the same endometrial tumor.
Somatic mitochondrial DNA (mtDNA) alterations including point mutations and microsatellite instability (MSI) have been frequently detected in human cancers. To further explore the extensiveness of mtDNA alterations, we have analyzed the occurrence of somatic mtDNA mutations in different populations of endometrial cancer cells from the same tumor tissues as compared with adjacent non-tumor cells. Laser-captured micro-dissection was used to harvest endometrial cancer cells from separated areas of the same tumor and adjacent normal cells. Total DNA isolated from micro-dissected cells was PCR amplified and analyzed for mtDNA alterations by polyacrylamide gel electrophoresis and DNA sequencing. Multiple mtDNA alterations were detected in different portions of the same tumor. Different populations of endometrial cancer cells carried different patterns of mtDNA mutations. Interestingly, unlike previous reports, most mutations were found to be heteroplasmic. We have demonstrated the occurrence of hyper-variability of mtDNA alterations in a single piece of tumor tissue. Our observations support the hypothesis that the accumulation of mtDNA alterations is random and expands independently. The data presented here showed the heterogeneity of cancer cells in terms of mtDNA alterations in endometrial cancer.
Wang
Yue
Y
Department of Obstetrics and Gynecology, People's Hospital, Peking University, Beijing, China.
Xue
Wei Cheng
WC
Liu
Vincent W S
VW
Ngan
Hextan Y S
HY
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007834:Lasers; D042282:Microdissection; D053842:Microsatellite Instability; D009030:Mosaicism; D017354:Point Mutation
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm