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Background  Whereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a  BRAF  mutation ( BRAF  mut ), unified biomarkers for the genetically heterogeneous group of  BRAF  wild type ( BRAF  wt ) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional  BRAF  wt  and  BRAF  mut  PTCs.    Methods  Microarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11  BRAF  wt  PTCs including five micro PTCs, 14  BRAF  mut  PTCs, and 7 normal thyroid specimens. A  p -value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data.  BRAF  mutational status was established by direct sequencing the hotspot region of exon 15.    Results  We identified 237 annotated genes that were significantly differentially expressed between  BRAF  wt  and  BRAF  mut  PTCs. Of these, 110 genes were down- and 127 were upregulated in  BRAF  wt  compared to  BRAF  mut  PTCs. A number of molecules involved in thyroid hormone metabolism including  thyroid peroxidase  ( TPO ) were differentially expressed between both groups. Among cancer-associated molecules were  ERBB3  that was downregulated and  ERBB4  that was upregulated in  BRAF  wt  PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set.    Conclusions  The expression study focusing on affected genes that are differentially expressed between  BRAF  wt  and  BRAF  mut  conventional PTCs identified a number of molecules which are connected in a network and affect important canonical pathways. The identified gene set adds to our understanding of the tumor biology of  BRAF  wt  and  BRAF  mut  PTCs and contains genes/biomarkers of interest.

Effect of BRAFmutational status on expression profiles in conventional papillary thyroid carcinomas