The mitochondrial DNA 4,977-bp deletion and its implication in copy number alteration in colorectal cancer

We conducted a comprehensive study on clinical features and mtDNA of 104 colorectal cancer patients in the Wenzhou area of China. In particular, using a quantitative real time PCR method, we analyzed the 4,977 bp deletion and mtDNA content in tumor tissues and paired non-tumor areas from these patients.We found that the 4,977 bp deletion was more likely to be present in patients of younger age (≤65 years, p = 0.027). In patients with the 4,977 bp deletion, the deletion level decreased as the cancer stage advanced (p = 0.031). Moreover, mtDNA copy number in tumor tissues of patients with this deletion increased, both compared with that in adjacent non-tumor tissues and with in tumors of patients without the deletion. Such mtDNA content increase correlated with the levels of the 4,977 bp deletion and with cancer stage (p < 0.001).Our study indicates that the mtDNA 4,977 bp deletion may play a role in the early stage of colorectal cancer, and it is also implicated in alteration of mtDNA content in cancer cells.Colorectal cancer is one of the leading human malignancies [1]. While its morbidity and mortality have declined in western countries in recent years, both the incidence and deaths caused by this cancer have increased significantly in recent years in Asia [2], particularly in China [3]. Both genetic and environmental factors contribute to colorectal cancer development. Based on a study on cohorts of twins from Sweden, Denmark and Finland, heritable factors contributed about 35% to colorectal cancer [4], while in another nationwide family study conducted with 9.6 million Swedish people, around 13% of colorectal susceptibility was attributed to genetic effects [5]. However, up to now, only 6% of colorectal cancer can be ascribed to mutations in particular genes [6]. Among those genes associated with predispositions for colorectal cancer are adenomatous polyposis coli (APC), a tumor suppressor involving cell adhesion, signal transduction and transcription activation,