Comprehensive analysis of the Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma

Timothy A. Dinh, Eva C.M. Vitucci, Eliane Wauthier, Rondell P. Graham, Wendy A. Pitman, Tsunekazu Oikawa, Mengjie Chen, Grace O. Silva, Kevin G. Greene, Michael S. Torbenson, Lola M. Reid, Praveen Sethupathy

Research output: Research - peer-reviewArticle

  • 2 Citations

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.

LanguageEnglish (US)
Article number44653
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 17 2017

Fingerprint

Untranslated RNA
Atlases
Genome
Carcinoma
Genes
Neoplasms
Long Noncoding RNA
Messenger RNA
Liver Neoplasms
RNA Sequence Analysis
Cholangiocarcinoma
Cyclic AMP-Dependent Protein Kinases
Oncogenes
Young Adult
Hepatocellular Carcinoma
Western Blotting
Immunohistochemistry
Gene Expression
Liver
Proteins

ASJC Scopus subject areas

  • General

Cite this

Comprehensive analysis of the Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. / Dinh, Timothy A.; Vitucci, Eva C.M.; Wauthier, Eliane; Graham, Rondell P.; Pitman, Wendy A.; Oikawa, Tsunekazu; Chen, Mengjie; Silva, Grace O.; Greene, Kevin G.; Torbenson, Michael S.; Reid, Lola M.; Sethupathy, Praveen.

In: Scientific Reports, Vol. 7, 44653, 17.03.2017.

Research output: Research - peer-reviewArticle

Dinh, TA, Vitucci, ECM, Wauthier, E, Graham, RP, Pitman, WA, Oikawa, T, Chen, M, Silva, GO, Greene, KG, Torbenson, MS, Reid, LM & Sethupathy, P 2017, 'Comprehensive analysis of the Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma' Scientific Reports, vol 7, 44653. DOI: 10.1038/srep44653
Dinh TA, Vitucci ECM, Wauthier E, Graham RP, Pitman WA, Oikawa T et al. Comprehensive analysis of the Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. Scientific Reports. 2017 Mar 17;7. 44653. Available from, DOI: 10.1038/srep44653
Dinh, Timothy A. ; Vitucci, Eva C.M. ; Wauthier, Eliane ; Graham, Rondell P. ; Pitman, Wendy A. ; Oikawa, Tsunekazu ; Chen, Mengjie ; Silva, Grace O. ; Greene, Kevin G. ; Torbenson, Michael S. ; Reid, Lola M. ; Sethupathy, Praveen. / Comprehensive analysis of the Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma. In: Scientific Reports. 2017 ; Vol. 7.
@article{6dd1aec2d63a417fb31c38f05c1124af,
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.",
author = "Dinh, {Timothy A.} and Vitucci, {Eva C.M.} and Eliane Wauthier and Graham, {Rondell P.} and Pitman, {Wendy A.} and Tsunekazu Oikawa and Mengjie Chen and Silva, {Grace O.} and Greene, {Kevin G.} and Torbenson, {Michael S.} and Reid, {Lola M.} and Praveen Sethupathy",
year = "2017",
month = "3",
doi = "10.1038/srep44653",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Comprehensive analysis of the Cancer Genome Atlas reveals a unique gene and non-coding RNA signature of fibrolamellar carcinoma

AU - Dinh,Timothy A.

AU - Vitucci,Eva C.M.

AU - Wauthier,Eliane

AU - Graham,Rondell P.

AU - Pitman,Wendy A.

AU - Oikawa,Tsunekazu

AU - Chen,Mengjie

AU - Silva,Grace O.

AU - Greene,Kevin G.

AU - Torbenson,Michael S.

AU - Reid,Lola M.

AU - Sethupathy,Praveen

PY - 2017/3/17

Y1 - 2017/3/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85015786590&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015786590&partnerID=8YFLogxK

U2 - 10.1038/srep44653

DO - 10.1038/srep44653

M3 - Article

VL - 7

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 44653

ER -