ECE2014 Oral Communications Neuroendocrinology & Signalling (5 abstracts)
NTRK3 receptor expression is strictly associated with medullary thyroid cancer RET mutation status
Malgorzata Oczko-Wojciechowska 1 , Michal Swierniak 1, , Malgorzata Kowalska 1 , Agnieszka Pawlaczek 1 , Monika Kowal 1 , Tomasz Tyszkiewicz 1 , Jadwiga Zebracka-Gala 1 , Dagmara Rusinek 1 , Tomasz Gawlik 1 & Jolanta Krajewska 1
1Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland; 2Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
Aim of the study: Medullary thyroid cancer (MTC) occurs as hereditary and sporadic form. Hereditary type is a consequence of RET proto-oncogene germline mutations also somatic RET mutations are detectable in sporadic MTC tumors. There is a significant relation between site of mutation and the cancer phenotype as well as a clinical course of the MEN 2 Syndrome as a consequence of the different transforming potential of the RET gene mutations. The aim of study was to evaluate whether the differences in gene expression profile are related to the particular RET mutation
Methods: Fresh-frozen tumor samples from 34 MEN 2 patients and 21 RET negative MTC patients were collected. Germline mutation screening was performed according to standard algorithm, assumed analysis of exon 10, 11, 13, 14, 15 and 16. RET somatic mutations were analyzed among sporadic MTC patients and 21 exons of RET gene were sequenced. Gene expression profile were analyzed by using Gene Chip 1.0 ST Arrays (Affymetrix). Unsupervised analysis was carried out by hierarchical clustering. Selection of probe sets were performed using Welch t-test with FDR.
Results: Hierarchical clustering did not show any global differences in gene expression profile between type of RET mutation, however, supervised analysis revealed 10 genes differentially expressed between tumor samples with mutation at RET codon 634 and 918 of the RET gene. The most significant was NTRK3 gene. Samples with mutation at codon 918 were characterized with higher level of expression of NTRK3 gene. Also NTRK1 and NTRK2 were verified in our data, however, there were no significant changes observed between type of RET gene mutations.
Conclusions: In conclusion, RET mutation status was more significant for the overall transcriptome profile than the heredity aspect and NTRK3 gene showed the most distinct changes in expression between tumors with specific type of RET gene mutations.
Volume 35
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Endocrine Abstracts
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