Differential occurrence of microsatellite instability in mitochondrial genome of gynecological cancers

Abstract

To investigate the occurrence of mitochondrial microsatellite instability (mtMSI) in human primary ovarian, endometrial, cervical, and breast carcinomas, we screened 13 microsatellite regions in mtDNA of cancer tissues and their matched normal controls. Four out of 13 microsatellite markers that start at np303, np514, np965 and np16184, respectively, exhibited instability, indicated by change in length of short base-repetitive sequences of mtDNA relative to control. About 20.5% (16/78) ovarian cancer patients, 48.4% (30/62) endometrial cancer patients, 25.4% (18/71) cervical cancer patients and 27.5% (14/51) breast cancer patients carried one or more mtMSI. The frequency of mtMSI in endometrial cancer was significantly higher than in the other three types of cancer (P value=0.003; χ2=14.269; 3 df). In particular, mtMSI was frequently detected in the D-loop region. A relatively long C tract interrupted by a T residue is the mtMSI hotspot in all four types of cancer studied. The differential occurrence of the mtMSI in various cancer types suggests that the generation of mtMSI may vary from one cancer to another. It may be partly attribute to the different mtDNA repair efficient in various tissues. The relatively high prevalence of mtMSI may be a potential new tool for detection of human cancers.