Germinal mutations of RET, SDHB, SDHD, and VHL genes in patients with apparently sporadic pheochromocytomas and paragangliomas.
BACKGROUND
Pheochromocytomas and paragangliomas are derived from neural crest cells and are localized mainly in adrenal medulla and sympathetic or parasympathetic ganglia. They can be inherited (25%) and be part of multi-endocrine syndromes such as MEN2 syndrome, von Hippel-Lindau syndrome, pheochromocytoma/paraganglioma syndrome, neurofibromatosis type 1, and Sturge-Weber syndrome. Clinical presentation can sometimes be atypical and does not always allow proper diagnosis. In such situations, DNA analysis can be helpful, especially when the pheochromocytoma is the first and only symptom.


METHODS
We analyzed DNA from 60 patients diagnosed and treated in the Centre of Oncology with a diagnosis of pheochromocytoma or paraganglioma. DNA analysis was carried out for RET (exons 10, 11, 13, and 16), SDHB, SDHD, and VHL genes. Techniques used for the analysis were direct sequence analysis, MSSCP, and RFLP.


RESULTS
Germinal mutations were found in 16 patients (26,7%). Most frequent were mutations in RET proto-oncogene, followed by VHL gene, one mutation in SDHB, and one in SDHD genes. A comparison of some of the clinical features of both groups (with and without mutation) showed statistically significant differences.


CONCLUSIONS
The results of our study show that genetic predisposition is frequent in chromaffin tissue tumours, which indicates that DNA analysis is necessary in every case, also because of possible atypical clinical presentation. (Pol J Endocrinol 2010; 61 (1): 43-48).
Krawczyk
Aleksandra
A
Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice Branch, Poland. akrawczyk@io.gliwice.pl
Hasse-Lazar
Kornelia
K
Pawlaczek
Agnieszka
A
Szpak-Ulczok
Sylwia
S
Krajewska
Jolanta
J
Paliczka-Cieślak
Ewa
E
Jurecka-Lubieniecka
Beata
B
Roskosz
Józef
J
Chmielik
Ewa
E
Ziaja
Jacek
J
Cierpka
Lech
L
Peczkowska
Mariola
M
Preibisz
Aleksander
A
Januszewicz
Andrzej
A
Otto
Maciej
M
Jarzab
Barbara
B
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D002648:Child; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics* / Q000556:secondary; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human