Cellular Pathogenesis of Fibrolamellar Hepatocellular Carcinoma

项目摘要 纤维板层型肝细胞癌（FLHCC）是一种常见的致死性疾病， 儿童和年轻人。预后差的原因是缺乏敏感的非侵入性诊断， 测试和缺乏针对性的系统治疗。我们最近展示了一个单一的，一致的 FLHCC患者的19号染色体的一个拷贝中的缺失导致嵌合基因。这编码了一个 由热休克蛋白DNAJB1的氨基末端部分融合到 蛋白激酶A的活性催化亚基。该项目将确定这种嵌合体是否足以 转化细胞然后，它将确定嵌合体诱导后细胞变化的程度， 开始阐明这些变化的途径和机制。

PROJECT SUMMARY Fibrolamellar hepatocellular carcinoma (FLHCC) is an often-lethal disease affecting primarily children and young adults. The poor prognosis stems from both the lack of sensitive non-invasive diagnostic tests and the lack of a targeted systemic therapy. We have recently demonstrated a single, consistent deletion in one copy of chromosome 19 of FLHCC patients that results in a chimeric gene. This encodes a chimeric protein comprised of the amino terminal portion of the heat shock protein DNAJB1 fused to the active catalytic subunit of protein kinase A. This project will determine if this chimera is sufficient for transforming cells. It will then determine the extent of cellular changes upon induction of the chimera and begin to elucidate the pathways and mechanisms for these changes.