Mutations in the MT-CYB Mitochondrial Gene in Prostate Tumors in Senegal: Molecular Analysis and Computational Prediction of Functional and Structural Effects

The prostate is affected by two types of tumors: benign prostatic hyperplasia and prostate cancer. These are the most commonly diagnosed tumors worldwide. Given the significance of mitochondrial genome alterations in cancerous lesions, this study aims to determine the characteristics of MT-CYB gene mutations in prostate tumors in Senegalese men. Twenty-seven biopsies were selected for the study. Mitochondrial DNA (MTCYB gene) was extracted, amplified by PCR, and sequenced. Mutations were detected using the Mutation Surveyor software. The pathogenicity of the variants was assessed using Polyphen-2, Provean, and SNPs & GO. The impact on protein stability and molecular mechanisms was evaluated using I Mutants 2.0, MuPro, and MutPred2. Mutation3D was used to map the identified high-risk non-synonymous mutations. The results revealed 125 mutations, predominantly found in malignant tissues. Thirteen mutations are shared by both tumours, suggesting their potential role as early biomarkers of prostate cancer risk. The prediction tools identified 75 potentially pathogenic mutations. All of the non-synonymous mutations affect protein stability. Among them, 14 alter molecular mechanisms, and 16 are classified as high-risk. Although the sample size is small, these results confirm that mutations in the MT-CYB gene contribute to prostate tumorigenesis.

Keywords: Prostate, Cancer, MT-CYB, Benign Hypertrophy, Mutations, Senegal.