RET is expressed but not mutated in extra-adrenal paragangliomas.
This study has investigated the role of the RET proto-oncogene, which has been identified as the susceptibility gene for multiple endocrine neoplasia (MEN) type 2, in the development of sporadic and familial extra-adrenal paragangliomas. RET protein expression was analysed by immunohistochemistry. Subsequently, DNA extracted from 52 tumours of 44 patients was screened for somatic RET point mutations in exons 10, 11, and 13-16, where oncogenic mutations have recently been described in a subset of sporadic medullary thyroid carcinomas and phaeochromocytomas. The methods employed included non-isotopic polymerase chain reaction-based single strand conformation polymorphism (PCR-SSCP) analysis and heteroduplex gel electrophoresis, followed by direct sequencing of PCR products. RET protein expression was demonstrated in all ten paragangliomas tested. However, none of the familial or sporadic extra-adrenal paragangliomas contained somatic mutations in exons 10, 11, or 13-16 of the RET proto-oncogene, whereas control samples with known mutations in these exons exhibited the expected band shift, or yielded an additional band with retarded migration. Although paragangliomas exhibit RET protein expression, these data indicate that oncogenic RET proto-oncogene mutations do not appear to be generally important in the formation of sporadic paragangliomas.
de Krijger
R R
RR
Department of Pathology, Erasmus University and University Hospital, Rotterdam, The Netherlands. dekrijger@path.fgg.eur.nl
van der Harst
E
E
Muletta-Feurer
S
S
Bruining
H A
HA
Lamberts
S W
SW
Dinjens
W N
WN
Roth
J
J
Heitz
P U
PU
Komminoth
P
P
D000328:Adult; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila