Genetic Variations of Mitochondrial Cytochrome B and Breast Cancer

The role of mitochondria encoded cytochrome b (cyt b) gene mutations has been drawn a great interest to understand the function of this gene in various cancer including breast cancer. Although most cancer cells harbor somatic mutations in mitochondrial DNA (mtDNA) including cytochrome b gene, the question of whether such mutations in cyt b contribute to the promotion of breast cancer remains obscured. In this study, we investigated the frequency of mutations in cyt b gene in forty (n = 40) breast cancer patients of Bangladesh. The results were compared with forty eight age matched control samples (n = 48) from our database. Nine (9) different sequence variations were found on cyt b genein cancer samples. Detail study of cyt b gene of forty eight (n = 48) controls found eighteen (n = 18) different variations, which demonstrates the high variability of cyt b sequence. Three of these eighteen mutations 15055 (G>A), 15301 (G>A), and 16326 (A>G) are also found in cancer patients. Two mutations in breast cancer patients were homoplasmic and identified as major percentage compared to control samples. Two mutations have been identified at np 14766 (C>T) 100%, followed by 14783 (T>C) in 40%breast cancer samples. Two other mutations at np15479 (T>C) and 15497 (G>A) have been reported in 2% breast cancer patients but absent from control samples. Three phylogenetic variations at np15055 (T>C), 15301 (G>A) and 15326 (A>G) have been found in 18% cancer patients respectively but also found in control samples. We have identified two insertion polymorphisms at 15970 (A-ins) and 15980 (T-ins) in 2% cancer samples. Thus, we hypothesized that mutation at np 14766 (C>T) 100% in cyt b gene may cause defective assembly and function of complex- III which thus hampers ATP production in cancer cells in addition with others mechanisms of breast cancer development. As a result, cancer cells are forced to use glycolytic pathways for ATP production. Alternatively two mutations14766 (C>T) and 15326 (G>A) lead to frame shift in amino acids (T7I) and (T194A) of translated protein. However report from the software analysis suggests that this (T7I) change might not be tolerated in protein function with some deleterious effect.