Expression profiling reveals a distinct transcription signature in follicular thyroid carcinomas with a PAX8-PPAR(gamma) fusion oncogene.
The demonstration of the PAX8-PPAR(gamma) fusion oncogene in a subset of follicular thyroid tumors provides a new and promising starting point to dissect the molecular genetic events involved in the development of this tumor form. In the present study, we compared the gene expression profiles of follicular thyroid carcinomas (FTCs) bearing a PAX8-PPAR(gamma) fusion against FTCs that lack this fusion. Using unsupervised clustering and multidimensional scaling analyses, we show that FTCs possessing a PAX8-PPAR(gamma) fusion have a highly uniform and distinct gene expression signature that clearly distinguishes them from FTCs without the fusion. The PAX8-PPAR(gamma)(+) FTCs grouped in a defined cluster, where highly ranked genes were mostly associated with signal transduction, cell growth and translation control. Notably, a large number of ribosomal protein and translation-associated genes were concurrently underexpressed in the FTCs with the fusion. Taken together, our findings further support that follicular carcinomas with a PAX8-PPAR(gamma) rearrangement constitute a distinct biological entity. The current data represent one step to elucidate the molecular pathways in the development of FTCs with the specific PAX8-PPAR(gamma) fusion.
Lui
Weng-Onn
WO
Department of Molecular Medicine, Karolinska University Hospital, Solna, CMM L8:01, SE-171 76 Stockholm, Sweden. weng-onn.lui@cmm.ki.se
Foukakis
Theodoros
T
Lidén
Johan
J
Thoppe
Srinivasan R
SR
Dwight
Trisha
T
Höög
Anders
A
Zedenius
Jan
J
Wallin
Göran
G
Reimers
Mark
M
Larsson
Catharina
C
D018263:Adenocarcinoma, Follicular / Q000175:diagnosis / Q000235:genetics*; D000429:Alcohol Oxidoreductases; D056970:Co-Repressor Proteins; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics; D003937:Diagnosis, Differential; D015536:Down-Regulation / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors; D014176:Protein Biosynthesis / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; D012269:Ribosomal Proteins; D015534:Trans-Activators; D000429:Alcohol Oxidoreductases; C421248:CTBP2 protein, human