38% 2-year recurrence- free survival, p=0. 0003). Principal Components Analysis discriminated cirrhotic and HCC Selisistat solubility dmso tissues, and HCC patients

with poor (<2 year) vs. good (>2 year) recurrence-free survival. Loss of CDH1 expression correlated with up-regulation of hepatocyte proliferation promoters MET and YAP1. CDH1, MET, and YAP1 were independent predictors of recurrence-free survival by Cox regression when corrected for tumor stage (p<0. 0001). Conclusion: HCV-cirrhosis is characterized by proliferation of liver stem cells and inhibition of hepatocyte proliferation. HCC tumors in which this pattern persists have superior outcomes to those which acquire a hepatocyte proliferation signature (loss of CDH1 and MST1, gain of MET, YAP1, MCM2). Genes in this signature should be studied further for potential as tissue or serum biomarkers for patient risk stratification. CDH1 and MET are candidates for personalized therapies with targeted pharmaceutical agents. Cox proportional hazards modeling of expression levels of proliferation genes, corrected for stage at diagnosis. The final model was highly significant (p<0. 0001) Parameter Parameter selleck products Estimate Chi-Square p-value Hazard Ratio Stage at diagnosis 1. 5 25. 5 <0. 0001 4. 48 CDH1 −1. 09 6. 75 0. 009 0. 34 MET 1. 11 3. 23 0. 07 3. 05 YAP1 1. 61 5. 74 0. 017

5. 01 Disclosures: The following people have nothing to disclose: Martha K. Behnke, Mark Reimers, Robert A. Fisher INTRODUCTION: Intrahepatic Cholangiocarcinoma (ICC) is a rare bile duct cancer with dismal prognosis. Fusion events are among the most potent oncogenic drivers, MCE and recent studies report dramatic therapeutic responses blocking these targets in melanoma and lung cancer. We aimed to identify fusion events that meaningfully contribute to ICC pathogenesis. METHODS: We analyzed a cohort of 115 ICC cases: 7 ICC

fresh-frozen paired samples were screened for fusion events using RNA-seq (HiSeq2000sequencer), and 108 paraffin-embedded tissues were used to validate the finding by RT-PCR and sanger sequencing. To identify fusion events, raw cDNA reads were aligned to a reference genome, with subsequent filters applied via in-house methods. A fusion gene was selected based on the number of supporting reads and partner genes and validated in the same patient where it was identified. Whole-genome sequencing was run in the sample with the fusion event. NIH3T3 cells were stably transfected to over-express the full fusion gene. The effect of the fusion gene on cell migration was investigated in vitro (transwell assay). RESULTS: An interchromosomal event resulting in the formation of a fusion gene comprising portions of an oncogenic tyrosine kinase receptor, FGFR2 (10p12) and a gene involved in epithelial differentiation, PPHLN1 (12q12) was identified in 1 patient.