The increase of mitochondrial DNA content in endometrial adenocarcinoma cells: a quantitative study using laser-captured microdissected tissues.
OBJECTIVE
Microsatellite instability (MSI) is a frequent genetic event in the D-loop region (which controls mitochondrial DNA (mtDNA) replication) of mitochondrial genome of endometrial cancer. We therefore investigated the relationship between mtMSI and mtDNA content in endometrial cancer.


METHODS
Tumor tissues from 65 cancer patients and normal tissues from 41 non-cancer patients were used in this study. Pure endometrial adenocarcinoma cells and normal endometrial glandular epithelial cells were collected by laser capture microdissection, and analyzed for levels of mtDNA copy number by real-time quantitative PCR.


RESULTS
Our data show that mtDNA copy number was not related with age in both endometrial cancer and normal endometrium cells. Great inter-individual variations in mtDNA copy number in endometrial cancer group were found; and mtDNA content was significantly larger than that in normal endometrium group. About 2-fold increase of mtDNA copy number was found in endometrial adenocarcinoma compared with normal endometrial glandular epithelium (P = 0.001). In particular, the analysis also shows that the copy number of mtDNA in the cases that carried the mtMSI at nucleotide position 303 was significantly higher than that of the negative cases (P = 0.048).


CONCLUSIONS
Our data indicate that mtDNA copy number increased during endometrial cancer development. There is also a correlation between the mtDNA instability and mtDNA content in endometrial cancer cells. Role of mitochondrial genome changes in carcinogenesis warrants further investigation.
Wang
Yue
Y
Departments of Obstetrics and Gynaecology, University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Liu
Vincent W S
VW
Xue
Wei-Cheng
WC
Tsang
Percy C K
PC
Cheung
Annie N Y
AN
Ngan
Hextan Y S
HY
D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005914:Globins / Q000235:genetics; D006801:Humans; D007206:Individuality; D042282:Microdissection; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004272:DNA, Mitochondrial; D005914:Globins