Mitochondrial DNA content in plasma associated with head and neck squamous cell carcinoma Free

2007

Prior work has demonstrated that malignancies shed their DNA into different tissue compartments at detectable levels. In head and neck squamous cell carcinoma (HNSCC), studies have demonstrated alterations in mitochondrial DNA content. The purpose of the study is to determine if mitochondrial DNA content is altered in a detectable fashion in the plasma of head and neck cancer patients versus case-matched negative controls. Additionally, in vitro experiments were conducted to elucidate if DNA shed from cells in culture had an altered mtDNA to nuclear DNA ratio. Plasma DNA was extracted from tissue samples of 43 individuals presenting with squamous cell head and neck cancer and 43 case-matched controls from a cancer-screening cohort. Samples were subjected to quantitative real-time PCR of mitochondrial genomic targets (COXI and COXII) and a nuclear genomic target (beta-actin). Mean content levels of Cox I and Cox II (log average of -1.78 and -1.94, respectively) in plasma samples were significantly lower in HNSCC patients compared with case-matched normal controls (log average of -0.41 and -0.20, respectively), which using a univariate regression model was significant, p values of <0.0001 for both Cox I and Cox II. Current smokers with HNSCC had a mean logarithmic level of Cox I of -2.69 and -2.95, significantly lower than their normal counterparts (Cox I of -0.40 and Cox II of -0.16), p value of 0.05 (Cox I) and 0.08 (Cox II) as well as significantly lower than the HNSCC patients who had not smoked (Cox I of -1.64 and Cox II of -1.80) and HNSCC patients who had quit smoking (Cox I of I -1.04 and Cox II of -1.10). O19 HNSCC cancer cells growing in culture preferentially shed nuclear DNA into the media during apoptosis. A similar phenomenon may account for the lower ratio found in tumor patient plasma.