CYTB: A HOT SPOT FOR PATHOGENIC MUTATIONS IN MITOCHONDRIAL GENOME OF BREAST CANCER AND OVARIAN CANCER PATIENTS
Objective: Out of various cancer types, Breast and ovarian cancers are the most commonly occurring malignancies in women. As per literature, a large number of mutations are reported in various mitochondrial genome encoded subunits of respiratory chain complexes in breast and ovarian cancer patients. However, a very few of them are functionally validated till now. Our study is an attempt to highlight the pathogenic potential of all these reported mutations in breast and ovarian cancer patients.
Methods: In order to achieve so, total 109mitochondrial gene mutations of breast cancer and 11 mitochondrial gene mutations of ovarian cancer patients were selected from MITOMAP database as well as various literatures. All these mutations were analyzed using various in silico tools such as MUSCLE, PolyPhen-2, SIFT, Mut Pred, Mu Pro, PANTHER, GOR4 and MUSCLE.
Results: As a result of our analysis, 28 out 95 mutations in CytB gene are most pathogenic in the case of breast cancer patients. On the other hand 2 out of 3 mutations of the same gene were predicted to be potentially pathogenic in case of ovarian cancer patients. Mutations in other mitochondrial subunit was also predicted pathogenic but with the low score.
Conclusion: Out of different mitochondrial subunits, CytB seems to most important site for mutations in these two groups of patients. Hence, mutations of CytB subunit, which are predicted to be highly pathogenic as per our analysis, should be functionally validated in future.
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