Differences in the transcriptome of medullary thyroid cancer regarding the status and type of RET gene mutations.
Medullary thyroid cancer (MTC) can be caused by germline mutations of the RET proto-oncogene or occurs as a sporadic form. It is well known that RET mutations affecting the cysteine-rich region of the protein (MEN2A-like mutations) are correlated with different phenotypes than those in the kinase domain (MEN2B-like mutations). Our aim was to analyse the whole-gene expression profile of MTC with regard to the type of RET gene mutation and the cancer genetic background (hereditary vs sporadic). We studied 86 MTC samples. We demonstrated that there were no distinct differences in the gene expression profiles of hereditary and sporadic MTCs. This suggests a homogeneous nature of MTC. We also noticed that the site of the RET gene mutation slightly influenced the gene expression profile of MTC. We found a significant association between the localization of RET mutations and the expression of three genes: NNAT (suggested to be a tumour suppressor gene), CDC14B (involved in cell cycle control) and NTRK3 (tyrosine receptor kinase that undergoes rearrangement in papillary thyroid cancer). This study suggests that these genes are significantly deregulated in tumours with MEN2A-like and MEN2B-like mutations; however, further investigations are necessary to demonstrate any clinical impact of these findings.
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Malgorzata
M
Oczko-Wojciechowska
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.|Genomic Medicine, Medical University of Warsaw, Warsaw, Poland.
Michal
M
Swierniak
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Jolanta
J
Krajewska
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Malgorzata
M
Kowalska
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Monika
M
Kowal
Department of Clinical Science, University of Bergen, Bergen, Norway.
Tomasz
T
Stokowy
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Bartosz
B
Wojtas
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Dagmara
D
Rusinek
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Agnieszka
A
Pawlaczek
The Oncology and Reconstructive Surgery Clinic, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Agnieszka
A
Czarniecka
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Sylwia
S
Szpak-Ulczok
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Tomasz
T
Gawlik
Tumour Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Ewa
E
Chmielik
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Tomasz
T
Tyszkiewicz
Tumour Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Barbara
B
Nikiel
Tumour Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Dariusz
D
Lange
III Radiotherapy Clinic, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Michal
M
Jarzab
College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Malgorzata
M
Wiench
Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland.
Barbara
B
Jarzab
D000328:Adult; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000473:pathology; D000070820:Discoidin Domain Receptor 2 / Q000032:analysis* / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000032:analysis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
C000715470:MAS1 protein, human; D008565:Membrane Proteins; C490237:NNAT protein, human; D009419:Nerve Tissue Proteins; D000090063:Proto-Oncogene Mas; C000603239:DDR2 protein, human; D000070820:Discoidin Domain Receptor 2; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C474200:CDC14B protein, human; D054637:Dual-Specificity Phosphatases