e18028 Background: Brain metastases (BM) occur in 30-50% of non-small cell lung cancer (NSCLC) patients and confer worse prognosis and quality of life. Better selection of in-risk patients through an accurate biomarker could improve the benefit of prophylactic therapies. The aim of this prospective study was to determine a gene-expression profile (GEP) of primary tumor (PT) associated with BM in patients with advanced NSCLC. Methods: From January 2009 to June 2011, patients with stage IV of NSCLC were evaluated. PT core biopsy was performed prior to any treatment and snap-frozen. Samples with tumor cellularity > 70% and RNA integrity number > 8 were chosen for RNA isolation. A cDNA microarray platform representing 33,297 genes was used to obtain GEPs. All patients received standard chemotherapy. BM were confirmed by magnetic resonance imaging. Non- and supervised hierarchical clustering methods were employed to identify GEPs. Results: A total of 29 patients were enrolled, 79.4% (23/29) were adenocarcinomas, and 20.6% have other histology. BM were present in 15 (51.7%) patients, 14 at diagnosis and 1 was developed at 5 months of follow-up. Clinical characteristics were similar for patients with and without BM. At non- and supervised analyses, 35 genes up and down regulated were evidenced in BM group. From these, 11 transcripts with proteomic functions previously associated with metastasis processes were identified. Conclusions: Our work provides valuable biological information for development of predictive biomarkers for metastatic brain tumors from primary NSCLC. External validation of our gene-expression signature in a different set of patients is warranted. [Table: see text]