Residual samples were tested for somatic mutations in hot spot regions of 50 common cancer related signaling pathway genes using Ion AmpliSeq™ Cancer Hotspot Panel v2 (Ion

TorrentTM). Illumina MiSeq sequencing was performed to confirm somatic alterations identified with Ion AmpliSeq. Results: Of the 92 patients, 54 had malignant (40 CCA [35 perihilar, 4 distal, 1 intrahepatic], 7 pancreas and 7 other cancers) and 38 had benign biliary strictures on clinicopathologic follow-up. Cytology and/or FISH were positive in 25/40 (63%) of CCA cases on follow-up. There were 24, 15 and 25 patients in the PSC without CCA, PSC-related CCA, and non-PSC related CCA groups with mean ages of 47, 52 and 67, respectively. At least 1 somatic

mutation was found in 19/40 (48%) CCAs. A significantly larger number of patients had detectable somatic tumor mutations in the non-PSC related CCA group than in the PSC-related CCA group (16/25 (64%) vs. 3/15 (20%), p=0.006). Mutation findings were similar in the subset of brushings with corresponding positive cytology/FISH results (8 PSC-related CCA and 17 non-PSC related CCA) (Table). Conclusions: Ibrutinib Mutations in TP53 and KRAS are the most commonly identified mutations in both PSC and non-PSC related CCA, but the mutation is less frequent in PSC. Epigenetic changes might be more important in PSC. Comprehensive genomic and genetic studies of PSC-re-lated CCA are required to elucidate the cholangiocarcinogen-esis pathways in PSC. Disclosures: Kevin C. Halling – Grant/Research medchemexpress Support: Abbott Molecular, Inc.; Patent Held/ Filed:

Abbott Molecular, Inc. Lewis R. Roberts – Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals, BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences Benjamin R. Kipp – Grant/Research Support: Abbott Molecular Inc. The following people have nothing to disclose: Roongruedee Chaiteerakij, Emily G. Barr Fritcher, Jesse Voss, Fergus J. Couch Background and Aim: Chromosome loci with genomic imbalance have been identified frequently in hepatocellular carcinoma (HCC). It is known that over two thirds of HBV-related HCCs originate in liver cirrhosis after a long duration up to several decades. However, it remains unclear that if the genomic imbalance may occur and accumulate in dysplastic hepatocytes of cirrhotic liver during the process from regenerated nodules to preneoplastic lesions,i.e.dysplastic nodule (DN).