Mtdna Mutations Associated With Breast Cancer Research

[Objective]To investigate the somatic mutations in control region of mitochondrial DNA (mtDNA) in patients with breast tumor in Yunnan Province.[Methods]The genomic DNA of tumor tissue and peripheral blood in28breast cancer patients and25benign breast tumor patients were extracted. mtDNA D-loop region (including its HVR1and HVR2) of each sample was amplified and sequenced with two pairs of primers. The somatic mutations were identified by comparing the mutation spectra between tumor tissue and peripheral blood.[Results]Totally,8somatic mutations were found in28breast cancer patients, including309+CC (sample BC6),309+C (sample BC20, sample BC26),279Y (sample BC16),297R (sample BC16),214R (sample BC21),190Y (sample BC61) and204Y (sample BC64);2somatic mutations in25benign breast tumor patients were found, including16292Y (sample BCA10) and309+CC (sample BCA12). Further analysis revealed that somatic mutations occurred more frequently in breast cancer patients (28.6%) than in benign breast tumor (15.4%)(P=0.03).We analyze the somatic mutations,immunhistochemistry of tumor's estrogen receptor,gene of HER-2and the lymph node metastasis of bilateral axillary in28breast cancer patients.Finally,we found that there were some relationship between somatic mutations and estrogen receptor expression. [Conclusion]Our data suggest that somatic mutations in mtDNA D-loop HVR1and HVR2may play some role in the pathogenesis of breast cancer, at least in the patients form Yunnan Province.Others,we didn't found the mtDNA haplogroup had significant correlation of breast tumor,combined with other studies,we can conclude that maternal genetic effect is small in breast tumor.In view of the relationship between somatic mutations and estrogen receptor expression,we can concluded if increase the number of sample,it can further study the relationship between somatic mutations and breast caner by estrogen receptor. [Objective]To investigate on the potential role of mtDNA somatic mutations in benign breast disease based on the entire mtDNA genome study,found out the relationship between benign breast disease and breast cancer.[Methods]The genomic DNA of tumorous tissue and peripheral blood in28benign breast disease patients were extracted respectively. The mtDNA whole genome was amplified into two overlapping segments, which were then sequenced respectively by using inner primers. Variants of each mtDNA genome were recorded according to the revised Cambridge reference sequence. The private variation (of each tumor tissue) was pinpointed by means of phylogenetic tree reconstruction, which was then screened in the mtDNA from the matched peripheral blood, with especial attention to verify whether the distilled variation is private to the patient or in fact specific to the tumor issue (viz. somatic variation).[Results]Based on the obtained mutation spectrum of mtDNA genomes, the phylogenetic tree was then reconstructed to identify their haplogroup status.Our results revealed7somatic mutations among the tissues of the28patients, among which1mutation locates in the control region whereas the rest6lie in the coding region. Further analyses revealed that, out of these6coding-region mutations,4are non-synonymous and will introduce change of AA.[Conclusion]Based on the extensively study on the mtDNA genomes from the issues of28benign breast disease patients, our current report observed a number of7somatic mutations. With the exception of16292that locates in the control region, the rest6are distributed in coding region, and most of which (4/6) are non-synonymous substitutions and will lead to the change of amino acid, indicating that these mtDNA mutations likely have some functional potential in tumorigenesis. Most significantly, our study further suggests the particular necessity of taking the entire genome of mtDNA into consideration during the study of tumorigenesis.Our topic based on genome-wide information's effect of mtDNA in breast disease,we could get the result that mtDNA matation may play an important role in the development of breast disease.Also,these mtDNA matation may could provide valuable genetic markers in clinical diagnosis of breast disease.The benign breast disease patient who accompanied by risk factors of breast cancer,their mtDNA somatic mutations were more than the perosn who didn't companied.In this regard,we look forward to further research.