DNA aberrations in an atypical skin cancer cohort
This study endeavoured to analyse whole blood derived samples for DNA aberrations in genes associated with tumour development and cellular maintenance, with the ultimate aim of identifying genes associated with non-melanoma skin cancer development. The blood-derived DNA (lymphocytic DNA) to be analysed in this study came from the 1996 Nambour Skin Cancer Trial, with 135 affected Solar Keratosis (SK) samples and 144 control samples analysed utilising non-specific fluorophoric Real-Time PCR for genetic aberrations. This study had an explicit emphasis on the mitochondrial genome and nuclear genes that encode for subunits in the mitochondrial regulated energy transducing oxidative phosphorylation pathways. More specifically, the aim of this project was to analyse the NDUFA8, PTCH, NDUFA5, SMOH, SDHD, MMP12, NDUFV1, EMS1, COXVIIc, and RASA1 genes via non-specific fluorophoric Real-Time PCR for genetic aberrations in an affected Solar Keratosis and control cohort.
The observation of putative aberrants in the NDUFV1, EMS1, COXVIIc, and RASA1 genes in the affected Solar Keratosis (SK) population was significantly higher than that observed in the control population, with an example being a difference of 30 % to 0.7% (p > 0.001) and 24% to 0.0% (p > 0.009) in the affected versus control SK COXVIIc and RASA1 cohort respectively.
The lymphocyte gene aberrations identified in this study may represent constitutive mutations and thus could pre-dispose an individual to developing SK. If the lymphocyte mutations were in the form of genetic risk factors, they could manifest themselves through a mitochondrial-driven mechanisms (such as the suppression of apoptosis) and could arise de novo or through inheritance in an autosomal dominant fashion. This mutation model still allows for other factors such as immunosuppression or exposure to topical carcinogens, which may explain why some individuals with lymphocytic gene aberrations may develop SK whilst others do not.