Mitochondrial D310 instability in Asian Indian breast cancer patients

Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various tumors. Mitochondrial D-loop is a non-coding region in the mitochondrial genome, which has essential transcription and replication elements, and alterations in this region may affect both these processes. The D-loop has a poly-C tract (PCT) located between 303 and 315 nucleotides known as D310, which has been identified as a frequent hot spot mutation region in human neoplasia. In the present study, 77 pairs of breast tumor and adjacent non-tumorous tissue samples were analyzed by polymerase chain reaction-single-strand conformational polymorphism, restriction fragment length polymorphism, and sequencing to evaluate the frequency of D310 (PCT) mutations and its association with clinicopathologic parameters of breast cancer. Alterations were detected in 25 of 77 (32.5 %) breast cancer samples; these included 7/25 (28 %) cases with heteroplasmy. This is the first study from Asian Indian breast cancer (BC) patients indicating a relatively high frequency of D310 mutations, suggesting that mtDNA instability at D310 may be a common characteristic of BC. However, 66.7 % of the alterations were observed in stage II BC, indicating that this may be a more important change for early progression of the disease rather than its initiation.