ECE2007 Poster Presentations (1) (659 abstracts)
Initiating mutations of BRAF gene in papillary thyroid carcinoma and their relation to gene expression profile
Dagmara Rusinek 1 , Malgorzata Wiench 1 , Malgorzata Oczko-Wojciechowska 1 , Jadwiga Zebracka 1 , Malgorzata Kowalska 1 , Daria Handkiewicz-Junak 1 , Sylwia Szpak-Ulczok 1 , Ewa Chmielik 2 , Agnieszka Czarniecka 3 , Michal Jarzab 4 , Grzegorz Gala 1 , Elzbieta Gubala 1 & Barbara Jarzab 1
1Department of Nuclear Medicine and Endocrine Oncology; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; 2Department of Tumor Pathology; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; 3Department of Oncological Surgery; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; 4Department of Tumor Biology; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland.
Introduction: Discovery of V600E (BRAFT1799A) mutation in papillary thyroid carcinoma (PTC) widened our knowledge about mechanisms of its molecular initiation. It has been revealed that activating mutations of the BRAF kinase are much more frequent in PTC than RET rearrangements.
Aim of the study: Estimation of V600E BRAF mutation frequency in PTC and analysis of differences in gene expression profile between papillary thyroid carcinomas activated by various molecular events with particular consideration of age of the patients.
Material and methods: The analysis of frequency of BRAF mutation was carried out in 77 PTC tumors. In the collection of 45 of these tissues RET/PTC rearrangements were analyzed and gene expression profiles were previously obtained (Genechip, Affymetrix). Total RNA was extracted from postoperative tumor tissues, cDNA was synthesized by gene-specific primers. Exon 15 of the BRAF gene was amplified by PCR and analyzed by automated sequencing.
Results: The V600E mutation was detected in 54.5% cases of PTC whereas RET/PTC rearrangements were identified in 11/42 cases (we identified BRAFT1799A mutation in two patients with previously detected RET/PTC rearrangement). The frequency of the V600E mutation was the highest in patients older than 40 years (67% of cases). Patients below 21 years harbouring BRAFT1799A mutation constituted only 7%, in contrast to RET rearrangements which were more often found in young patients. Meta-analysis of our own microarray data and these published by Giordano et al., 2005, showed significant differences in gene expression profiles dependent on the type of initiating mutation in PTC. Genes specified by this analysis were subsequently validated by QPCR.
Conclusions: The frequency of BRAF mutation in PTC is almost two times higher than of RET rearrangements. The occurrence of these genetic alterations is age-dependent. The meta-analysis of PTC gene expression profiles indicates a distinct difference between BRAF-induced and RET-induced papillary thyroid cancers.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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