Examination of Smad2 and Smad4 copy-number variations in skin cancers

Abstract

Background Smad2 and Smad4 transcription factors were identified as the signalling mediators of transforming growth factor ß (TGF ß) pathway. Copy number variations (CNVs) have been discovered to have phenotypic consequences and be associated with various types of cancers. CNVs of Smad2 and Smad4 were found to be associated with cancer pathogenesis in the recent array-based study. However, no such study has been performed in skin cancer yet. In this study, we aim to examine the CNVs of Smad2 and Smad4 in skin samples. Methods A total of 195 paired samples including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and actinic keratosis (AK) were included. Real-time PCR was used for the quantification of Smad2 and Smad4 copy numbers. Results CNVs of Smad2 showed statistical differences between cancer samples (both SCC and BCC) and normal tissues (p<0.05). For Smad4, statistical difference was observed only in SCC samples (p=0.014), but not in BCC and AK samples (p=0.173 and 0.314, respectively). Association analysis showed that the frequencies of Smad2 and Smad4 CNVs were correlated with the severity of skin abnormalities (p=0.002 for Smad2 and p=0.029 for Smad4). Conclusions CNVs of Smad2 are associated with SCC and BCC, while CNVs of Smad4 are associated with SCC but not BCC.