Somatic mutations in
mitochondrial DNA (
mtDNA) have been identified in various
tumors, including
breast cancer. However, their clinicopathological impact on
breast cancer still remains unclear. In this study, we re-sequenced the entire
mtDNA from
breast cancer samples together with paired non-tumorous breast tissues from 58 Taiwanese patients. We identified 19 somatic mutations in the
mtDNA coding region of 16 breast
cancers. Out of these mutations, 12 of the 19 mutations (63%) are missense or frame-shift mutations that have the potential to cause
mitochondrial dysfunction. In combination with our previously study on the D-loop region of
mtDNA, we found that 47% (27/58) of the breast
cancers harbored somatic
mtDNA mutations. Among a total of 40 somatic mutations, 53% (21/40) were located in the D-loop region of the
mtDNA, 5% (2/40) were in the ribosomal RNA genes, 5% (2/40) were in the
tRNA genes, and 38% (15/40) occurred in
mRNA genes. The occurrence of these somatic
mtDNA mutations is associated with an older onset age (≥ 50-year old, P = 0.039), a higher TNM stage (P = 0.027), and a higher histological grade (P = 0.012). Multiple logistic regression analysis revealed that an older onset age (P = 0.029) and a higher histological grade (P = 0.006) are significantly correlated with patients having somatic mutations in the
mtDNA in their
breast cancer sample. In conclusion, our results suggest that somatic
mtDNA mutations may play a critical role in the progression of
breast cancer.