Profiling mitochondrial <scp>DNA</scp> mutations in tumors and circulating extracellular vesicles of triple‐negative breast cancer patients for potential biomarker development

Abstract Early detection and recurrence prediction are challenging in triple‐negative breast cancer (TNBC) patients. We aimed to develop mitochondrial DNA (mtDNA)‐based liquid biomarkers improve TNBC management. Mitochondrial genome (MG) enrichment next‐generation sequencing mapped the entire MG 73 samples (64 tissues 9 extracellular vesicles [EV] samples) from 32 metastatic TNBCs. measured mtDNA cardiolipin (CL) contents, NDUFB8, SDHB protein expression tumors corresponding circulating EVs. identified 168 nonsynonymous mutations, with 73% (123/186) coding 27% (45/168) noncoding nature. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) was key target, which harbored 44% (74/168) overall mutations. A panel 11 hotspot among 19%–38% TNBCs, detectable serum‐derived EVs 82% specificity. Overall, 38% tumor‐signature traceable An appreciable number homoplasmic (18%, 31/168), novel (14%, 23/168), potentially pathogenic (9%, 15/168). The RCI‐specific mutational load higher women African compared European ancestry accompanied by an exclusive abundance respiratory (RC) NDUFB8 (RCII) therein. Increased ( p &lt; 0.0001) content recorded both along CL = Aggressive mutation measurement contents bear potential formulate noninvasive early strategies.