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The prevalence of somatic RAS mutations in medullary thyroid cancer — a Polish population study
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Abstract
Introduction: Somatic RET mutations are detectable in two-thirds of sporadic cases of medullary thyroid cancer (MTC). Recent studies reported a high proportion of RAS somatic mutations in RET negative tumours, which may indicate RAS mutation as a possible alternative genetic event in sporadic MTC tumorigenesis. Thus, the aim of the study was to evaluate the frequency of somatic RAS mutations in sporadic medullary thyroid cancer in the Polish population and to relate the obtained data to the presence of somatic RET mutations.
Material and methods: Somatic mutations (RET, RAS genes) were evaluated in 78 snap-frozen MTC samples (57 sporadic and 21 hereditary) by direct sequencing. Next, three randomly selected RET-negative MTC samples were analysed by the next generation sequencing.
Results: RAS mutation was detected in 26.5% of 49 sporadic MTC tumours. None of all the analysed samples showed N-RAS mutation. When only RET-negative samples were considered, the prevalence of RAS mutation was 68.7%, compared to 6% observed in RET-positive samples. Most of these mutations were located in H-RAS codon 61 (72%). None of 21 hereditary MTC samples showed any RAS mutations.
Conclusions: RAS mutations constitute a frequent molecular event in RET-negative sporadic medullary thyroid carcinoma in Polish patients. However, their role in MTC tumorigenesis remains unclear. (Endokrynol Pol 2015; 66 (2): 121–125)
Abstract
Introduction: Somatic RET mutations are detectable in two-thirds of sporadic cases of medullary thyroid cancer (MTC). Recent studies reported a high proportion of RAS somatic mutations in RET negative tumours, which may indicate RAS mutation as a possible alternative genetic event in sporadic MTC tumorigenesis. Thus, the aim of the study was to evaluate the frequency of somatic RAS mutations in sporadic medullary thyroid cancer in the Polish population and to relate the obtained data to the presence of somatic RET mutations.
Material and methods: Somatic mutations (RET, RAS genes) were evaluated in 78 snap-frozen MTC samples (57 sporadic and 21 hereditary) by direct sequencing. Next, three randomly selected RET-negative MTC samples were analysed by the next generation sequencing.
Results: RAS mutation was detected in 26.5% of 49 sporadic MTC tumours. None of all the analysed samples showed N-RAS mutation. When only RET-negative samples were considered, the prevalence of RAS mutation was 68.7%, compared to 6% observed in RET-positive samples. Most of these mutations were located in H-RAS codon 61 (72%). None of 21 hereditary MTC samples showed any RAS mutations.
Conclusions: RAS mutations constitute a frequent molecular event in RET-negative sporadic medullary thyroid carcinoma in Polish patients. However, their role in MTC tumorigenesis remains unclear. (Endokrynol Pol 2015; 66 (2): 121–125)
Keywords
medullary thyroid cancer; RET; RAS; driver mutation
About this articleTitle
The prevalence of somatic RAS mutations in medullary thyroid cancer — a Polish population study
Journal
Issue
Article type
Original paper
Pages
121-125
Published online
2015-05-01
Page views
2699
Article views/downloads
3045
DOI
10.5603/EP.2015.0018
Pubmed
Bibliographic record
Endokrynol Pol 2015;66(2):121-125.
Keywords
medullary thyroid cancer
RET
RAS
driver mutation
Authors
Malgorzata Oczko-Wojciechowska
Aleksandra Pfeifer
Dagmara Rusinek
Agnieszka Pawlaczek
Jadwiga Zebracka-Gala
Malgorzata Kowalska
Monika Kowal
Michal Swierniak
Jolanta Krajewska
Tomasz Gawlik
Ewa Chmielik
Agnieszka Czarniecka
Sylwia Szpak-Ulczok
Barbara Jarząb
