Sccro/Dcun1d-Gene Family Is Commonly Dysregulated In Non-Small Cell Lung Cancers

22058 Background: SCCRO1/DCUN1D1 is a novel oncogene mapped to 3q26.3, a locus known to be amplified in a wide range of human cancers. SCCRO1 amplification is associated with an aggressive clinical course. In silico analyses identified four highly conserved SCCRO1 paralogs mapped to chromosomal loci known to be aberrant in malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to assess the status of the SCCRO/DCUN1D family in NSCLC by gene expression analysis and correlate with histological subtypes of NSCLC, clinical parameters and outcome. Methods: RNA was extracted from snap frozen primary lung cancer from 56 patients undergoing definitive resection following institutional guidelines and after obtaining informed consent (n=27 adenocarcinomas (ADC); n=30 squamous cell carinomas (SCC)). Specific primer pairs were designed. Gene expression analysis was performed using RT-PCR. GEnorm identified B-actin as the most stable housekeeping gene which was used as control. Change in gene expression was determined for each tumor relative to its matched normal tissue. All statistical comparisons were performed using non-parametric measures. Results: Four of the five SCCRO-family genes (SCCRO1, SCCRO2, SCCRO4 and SCCRO5) were overexpressed in NSCLC. Overexpression of these genes was significantly more common in SCC (57%, 23%, 7% and 47% respectively) relative to ADC (4%, 11%, 0% and 7% respectively), with 70% of SCC having at least one of these genes dysregulated. There was a postitive correlation for overexpression and history of smoking (p<0.05) and outcome (P=0.05) in SCC. The expression of SCCRO3R was significantly reduced in both ADC (48%) and SCC (57%), but showed no correlation with clinical or outcome variables. Conclusions: The SCCRO family of genes are overexpressed in a significant number of lung SCC, but not ADC. Overexpression is correlated with a history of tobacco exposure, implicating it as a putative tobacco-related event. Interestingly, there was a significant loss in expression of SCCRO3R in both ADC and SCC. Biochemical characteristization of SCCRO3R suggest it may act as an antagonist of the other SCCRO family members, suggesting its function as a tumor suppressor. The dysregulation of SCCRO in NSCLC may have diagnostic and therapeutic implications. No significant financial relationships to disclose.