The prevalence of somatic RAS mutations in medullary thyroid cancer - a Polish population study.
BACKGROUND
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.


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.
Department of Nuclear Medicine and Endocrine Oncology Maria Sklodowska-Curie memorial Cancer Center and Institute of Oncology in Warsaw, Gliwice Branch. gosiaoczko@io.gliwice.pl.
Malgorzata
M
Oczko-Wojciechowska
Aleksandra
A
Pfeifer
Dagmara
D
Rusinek
Agnieszka
A
Pawlaczek
Jadwiga
J
Zebracka-Gala
Malgorzata
M
Kowalska
Monika
M
Kowal
Michal
M
Swierniak
Jolanta
J
Krajewska
Tomasz
T
Gawlik
Ewa
E
Chmielik
Agnieszka
A
Czarniecka
Sylwia
S
Szpak-Ulczok
Barbara
B
Jarząb
D018278:Carcinoma, Neuroendocrine / Q000235:genetics*; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics*
D008565:Membrane Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human