GENETIC MUTATION PROFILE IN MITOCHONDRIAL DYNAMICS AND MITOPHAGY AMONG DIFFERENT TYPES OF CANCER

Mitochondria are organelles responsible for maintaining cellular homeostasis. However, disruption of this process contributes to tumor progression. The principal regulators of mitochondrial integrity include mitochondrial dynamics, which involve the fusion, fission, and transport of mitochondria, as well as mitophagy, which selectively degrades dysfunctional mitochondria. This study investigated genetic mutation profiles related to mitochondrial dynamics and mitophagy in advanced stages of breast (BC) and prostate cancers (PC). This in silico study analyzed cBioPortal databases, focusing on metastatic BC and PC. Genes associated with mitochondrial dynamics and mitophagy were selected using mitoXplorer 2.0. Samples were filtered by tumor type (primary, metastatic, and compared alterations). Mutation data were processed using R and RStudio. In analysis, missense mutations were predominant in both mitochondrial process genes, with consistent patterns observed between primary and metastatic BC and PC. In BC, USP8 and OPTN (mitophagy), and OPA1 (mitochondrial dynamics) showed mutations across both primary and metastatic stages. For PC, AMBRA1 (mitophagy) and KIF1B (mitochondrial dynamics) were recurrently mutated from primary to metastatic tumors in both metastatic BC and PC. The variant allele frequency (VAF) across all processes revealed subclonal patterns (VAF < 0.5) in both primary and metastatic BC and PC. Mitochondrial variant profiles revealed a significant increase in variant diversity in metastatic BC and PC tumors compared to corresponding primary tumors. Additionally, some variants were shared between the primary and metastatic stages of the same cancer type. The results suggest that mitochondrial alterations may favor mitochondrial adaptation and contribute to metastatic progression.