Curriculum in Genetics and Molecular Biology, Chapel Hill, NC, USA.
MD/PhD Program, Chapel Hill, NC, USA.
Sci Rep. 2017 Mar 17;7:44653. doi: 10.1038/srep44653.
Fibrolamellar carcinoma (FLC) is a unique liver cancer primarily affecting young adults and characterized by a fusion event between DNAJB1 and PRKACA. By analyzing RNA-sequencing data from The Cancer Genome Atlas (TCGA) for >9,100 tumors across ~30 cancer types, we show that the DNAJB1-PRKACA fusion is specific to FLCs. We demonstrate that FLC tumors (n = 6) exhibit distinct messenger RNA (mRNA) and long intergenic non-coding RNA (lincRNA) profiles compared to hepatocellular carcinoma (n = 263) and cholangiocarcinoma (n = 36), the two most common liver cancers. We also identify a set of mRNAs (n = 16) and lincRNAs (n = 4), including LINC00473, that distinguish FLC from ~25 other liver and non-liver cancer types. We confirm this unique FLC signature by analysis of two independent FLC cohorts (n = 20 and 34). Lastly, we validate the overexpression of one specific gene in the FLC signature, carbonic anhydrase XII (CA12), at the protein level by western blot and immunohistochemistry. Both the mRNA and lincRNA signatures support a major role for protein kinase A (PKA) signaling in shaping the FLC gene expression landscape, and present novel candidate FLC oncogenes that merit further investigation.
纤维板层样肝细胞癌（FLC）是一种独特的肝癌，主要影响年轻人，其特征是 DNAJB1 和 PRKACA 之间的融合事件。通过分析来自癌症基因组图谱（TCGA）的 >9100 个肿瘤的 RNA 测序数据，我们发现 DNAJB1-PRKACA 融合是 FLC 特有的。我们证明了 FLC 肿瘤（n=6）与最常见的两种肝癌（肝细胞癌，n=263；胆管癌，n=36）相比，表现出明显不同的信使 RNA（mRNA）和长基因间非编码 RNA（lincRNA）特征。我们还鉴定了一组 mRNAs（n=16）和 lincRNAs（n=4），包括 LINC00473，它们可以将 FLC 与~25 种其他肝脏和非肝脏癌症类型区分开来。我们通过对两个独立的 FLC 队列（n=20 和 34）进行分析，证实了这种独特的 FLC 特征。最后，我们通过 Western blot 和免疫组织化学验证了 FLC 特征中一个特定基因，碳酸酐酶 XII（CA12）的过度表达。mRNA 和 lincRNA 特征均支持蛋白激酶 A（PKA）信号在塑造 FLC 基因表达图谱方面的主要作用，并提出了值得进一步研究的新的候选 FLC 癌基因。
