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Expression analysis of B-Raf oncogene in V600E-negative benign and malignant tumors of the thyroid gland: correlation with late disease onset

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Abstract

B-Raf, a member of the Raf serine/threonine kinase family, is an intermediate molecule in the mitogen-activated protein kinase pathway, which relays extracellular signals from the cell membrane to the nucleus via a cascade of phosphorylation events, ultimately promoting cancer development. This pathway is usually activated in human neoplasias. The purpose of this study was to investigate the role of B-Raf in thyroid pathology. We scanned for the presence of mutations at codon 600 (V → E) of the B-Raf gene, using a PCR–RFLP assay. In tumors with no mutation (32 benign and malignant thyroid tumors) and in their adjacent normal tissue, we measured the expression levels of B-Raf gene, using a quantitative real-time PCR (qPCR) assay. B-Raf expression in V600E-negative tumors deviated from the normal pattern, since it was overexpressed in 42 % of benign samples and downregulated in 54 % of malignant specimens. Hashimoto’s thyroiditis also seemed to play an important role, since benign specimens with Hashimoto’s thyroiditis had a 2.2-fold higher B-Raf expression than samples without thyroiditis (1.71 ± 0.63 vs. 0.78 ± 0.13). Statistical analysis revealed that B-Raf deregulation postponed disease onset by more than 10 years in both benign and malignant thyroid (benign: 55.6 ± 3.9 vs. 45.3 ± 3.3, p = 0.049; malignant: 52.2 ± 3.5 vs. 33.0 ± 7.9, p = 0.020). From the above results, we deduce that in the absence of mutation activation, B-Raf overexpression or downregulation is a protective event, since it delays the development of both malignant and benign thyroid tumors.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Clinical Virology, Medical School, University of Crete, P.O. Box 2208, 71003, Heraklion, Crete, Greece

    Stavros P. Derdas, Nikolaos Soulitzis, Vasileios Balis & Demetrios A. Spandidos

  2. 4th Department of Surgery, Medical School, University of Athens, Athens, Greece

    Georgios H. Sakorafas

Authors
  1. Stavros P. Derdas
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  2. Nikolaos Soulitzis
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  3. Vasileios Balis
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  4. Georgios H. Sakorafas
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  5. Demetrios A. Spandidos
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Correspondence to Demetrios A. Spandidos.

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Derdas, S.P., Soulitzis, N., Balis, V. et al. Expression analysis of B-Raf oncogene in V600E-negative benign and malignant tumors of the thyroid gland: correlation with late disease onset. Med Oncol 30, 336 (2013). https://doi.org/10.1007/s12032-012-0336-3

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  • DOI: https://doi.org/10.1007/s12032-012-0336-3

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