title: Comprehensive analysis of The Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma.
abstract: 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.
authors.affiliation: Curriculum in Genetics and Molecular Biology, Chapel Hill, NC, USA.|MD/PhD Program, Chapel Hill, NC, USA.|Department of Genetics, Chapel Hill, NC, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Dinh
authors.affiliation: Department of Genetics, Chapel Hill, NC, USA.|Post-baccalaureate Research Education Program, Chapel Hill, NC, USA.
authors.forename: Eva C M
authors.initials: EC
authors.lastname: Vitucci
authors.affiliation: Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Eliane
authors.initials: E
authors.lastname: Wauthier
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Rondell P
authors.initials: RP
authors.lastname: Graham
authors.affiliation: Department of Genetics, Chapel Hill, NC, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Pitman
authors.affiliation: Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Oikawa
authors.affiliation: Department of Genetics, Chapel Hill, NC, USA.|Department of Biostatistics, Chapel Hill, NC, USA.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Genetics, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Curriculum in Bioinformatics and Computational Biology, Chapel Hill, NC, USA.
authors.forename: Grace O
authors.initials: GO
authors.lastname: Silva
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Greene
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Torbenson
authors.affiliation: Department of Cell Biology and Physiology and Program in Molecular Biology and Biotechnology, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Lola M
authors.initials: LM
authors.lastname: Reid
authors.affiliation: Curriculum in Genetics and Molecular Biology, Chapel Hill, NC, USA.|Department of Genetics, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D015894:Genome, Human; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015854:Up-Regulation / Q000235:genetics
chemical_list: D062085:RNA, Long Noncoding; D012333:RNA, Messenger