Multicancer Study Links Mitochondrial DNA Copy Number to Tumor Mutational Burden

Overview

• A large multicancer analysis published Wednesday found that higher mitochondrial DNA (mtDNA) copy number closely correlates with greater tumor mutational burden across many cancer types.
• Predictive models in the study ranked mtDNA copy number and the count of mutated mitochondria-localized genes as top predictors of expression changes in cancer hallmark pathways.
• Tumors with low mtDNA tended to show higher expression of cancer-promoting programs such as cell migration and epithelial–mesenchymal transition, while some high-mtDNA tumors showed upregulation of tumor suppressor and chemotherapy-response genes.
• The relationship varied by cancer type and persisted after adjusting for tumor ploidy, meaning chromosomal copy number partly explains the pattern but does not fully account for it.
• Because mitochondria have their own genome that controls key energy and stress functions, the authors say these findings point to mtDNA measures as candidate biomarkers and call for lab experiments, prospective patient studies, and clinical tests to confirm whether mtDNA can guide treatment.