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DOI: 10.1055/s-0029-1215558
© Georg Thieme Verlag KG Stuttgart · New York
Lack of Correlation between BRAF V600E Mutational Status and the Expression Profile of a Distinct Set of miRNAs in Papillary Thyroid Carcinoma
Publication History
received 13.01.2009
accepted 11.02.2009
Publication Date:
15 April 2009 (online)
![](https://www.thieme-connect.de/media/hmr/200906/lookinside/thumbnails/10.1055-s-0029-1215558-1.jpg)
Abstract
Recent studies demonstrated a significant upregulation of distinct microRNAs (miRNAs), small endogenous RNAs that regulate gene expression, in papillary thyroid carcinoma (PTC). In the pathogenesis of PTC the T1799A (V600E) BRAF mutation is the most common genetic alteration leading to a constitutive activation of the MAPK pathway. The aim of the present study was to elucidate a possible correlation between BRAF mutational status and a distinct miRNA expression profile. In a series of 221 PTC we determined the BRAF V600E mutational status using DNA-sequencing and correlated the occurrence of the mutation with a variety of clinicopathologcial data. The miRNA expression profile of five selected subtypes (miRNA-146b, −181b, −21, −221, −222) in two matched cohorts of BRAF positive (n=28) and wildtype cases (n=26) was examined by RT-PCR TaqMan miRNA assay. The BRAF V600E mutation was significantly found in PTCs with extrathyroidal extension (p <0.001). Among them, V600E was even significantly associated with smaller tumour size of 1 cm or less (microcarcinomas; p<0.003) and the follicular (p=0.017) and tall cell variant (p=0.015). By calculating relative changes in miRNA gene expression no differences in fold changes could be detected between BRAF positive and wildtype PTC suggesting that BRAF has no regulatory influence on the expression of the five examined miRNAs. However, our study confirmed the diagnostic utility of this distinct set of miRNAs to detect PTC by significant fold changes in at least 3 miRNAs (miRNA-146b, −221, −222) irrespective of its histological variant.
Key words
miRNA - BRAF - papillary thyroid carcinoma
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Correspondence
K. W. Schmid MD, MRCPath
Institute of Pathology and Neuropathology
University Hospital of Essen
University of Duisburg-Essen
Hufelandstr. 55
45122 Essen
Germany
Phone: +49/201/723/2890
Fax: +49/201/723/5926
Email: kw.schmid@uk-essen.de