Introduction: Activating point mutations in the RAS genes (H-RAS, K-RAS, N-RAS) are reported in thyroid tumors. The aim of this study was to determine the frequency of RAS mutations in 98 patients with thyroid tumors.
Methods: DNA was extracted from 72 fresh frozen thyroid samples and 26 paraffin-embedded formalin-fixed samples. The cohort contained 83 PTCs (56 FVPTCs, 14 mixed follicular-classical types, 11 classical variants and two other rare variants), one FTA, 7 FTCs, 4 poorly differentiated carcinomas (PDC) and 3 anaplastic carcinomas (ATC). The presence of RAS mutations in exon 1 and exon 2 of the H-RAS, K-RAS, N-RAS genes was determined by direct sequencing and detected missence RAS alterations were evaluated in silico analysis using PolyPhen-2, Align-GVGD and SIFT software.
Results: Mutations in six PTC patients was found in codon 61 of the activating domain of K-RAS (2 patients) and N-RAS genes (4 patients). The polymorphism 81T-C in H-RAS gene was found in 41% PTC, in one FTA, 3 FTC, 3 PDC and one ATC. We detected other 7 silent, 6 missence and one nonsense genetic changes. The alterations were found only in follicular variant of PTC. The association with phenotype was not apparent.
Conclusion: RAS mutations in our cohort of thyroid cancer were screened. In addition to mutations in codon 61 (GTPase domain) in six patients, we revealed other genetic changes. However, their influence on the development of PTC needs to be confirmed.
Supported by IGA MH CR NR/9165-3 and CZ.2.17/1.1.00/32386.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
05 - 09 May 2012
European Society of Endocrinology