Abstract 3514: Assessing the role of CREB in fibrolamellar hepatocellular carcinoma with PRKACA-DNAJB1 fusion protein

Abstract Introduction: Fibrolamellar Hepatocellular Carcinoma (FLHCC) is a rare form of liver cancer that occurs predominantly in adolescents or young adults. Curing or prolonging the lives of patients with FLHCC is extremely challenging. Despite aggressive surgical resections of primary tumors as well as metastatic lesions, outcomes tend to be poor due to lack of effective chemotherapy. Previous studies have demonstrated the presence of PRKACA-DNAJB1 fusion protein in the majority of FLHCC patients. DNAJB1 is a heat shock protein and PKA is a kinase that phosphorylates numerous substrates including cAMP-regulatory element-binding protein (CREB), a proto-oncogenic transcription factor. Therefore, we sought to examine whether the presence of the fusion protein in FLHCC is associated with increased CREB phosphorylation. Methods: We analyzed tumor and matched non-neoplastic liver tissue from 7 pediatric patients with a pathologic diagnosis of FLHCC. We assessed the presence of the PRKACA-DNAJB1 fusion protein using PKA antibody, as well as total CREB and phosphorylated (p-CREB) using immunoblot analyses with specific antibodies. Results: Immunoblot analysis using anti-PKA antibody confirmed the occurrence of PRKACA-DNAJB1 fusion transcripts in 6/7 (86%) FLHCC tumor samples. Immunoblot analyses of the 6 patients with the fusion protein revealed a trend towards a decrease in p-CREB expression in tumor samples compared to non-neoplastic tissue controls (p=0.15). Conclusions: The pattern of p-CREB in FLHCC with PRKACA-DNAJB1 fusion protein suggests that the fusion protein does not exert its proto-oncogenic effects through the transcriptional activity of CREB. Citation Format: Anju Karki, Michael J. LaQuaglia, Amanda M. Dios, Ghazaleh Sadri-Vakili, Khashayar Vakili. Assessing the role of CREB in fibrolamellar hepatocellular carcinoma with PRKACA-DNAJB1 fusion protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3514. doi:10.1158/1538-7445.AM2017-3514