Absence of mutations in the MEN2A region of the ret proto-oncogene in non-MEN 2A phaeochromocytomas.
OBJECTIVE
To determine the presence of abnormalities of the MEN2A region of the ret proto-oncogene in phaeochromocytomas/paragangliomas (PHAEO) of different aetiologies.


METHODS
Total RNA was extracted from tumours and used as templates for reverse transcriptase polymerase chain reactions. A ret primer pair, which encompasses the region which is mutated in the germ-line of patients with MEN 2A, was used. The resulting 262-bp product was sequenced.


METHODS
Ten PHAEOs were examined. Four tumours were from von Hippel-Lindau disease patients; five were sporadic, isolated tumours; one from a patient with multiple endocrine neoplasia type 2A (MEN 2A). The medullary thyroid cancer from the single MEN 2A patient was also examined.


RESULTS
A heterozygous TGC to CGC mutation of codon 634 (cysteine to arginine) was found in the PHAEO and medullary thyroid cancer from the MEN 2A patient. The 262-bp ret fragment was not found in two tumours (one malignant PHAEO and one secretory paraganglioma), although the intra-cellular ret tyrosine kinase domain was detected in these tumours. The cysteine codons were normal in all other non-MEN 2A PHAEOs.


CONCLUSIONS
Mutations of key cysteine codons of the ret proto-oncogene may be specific to MEN 2A.
Chew
S L
SL
Department of Endocrinology, St Bartholomew's Hospital, London, UK.
Lavender
P
P
Jain
A
A
Weber
A
A
Ross
R J
RJ
Wass
J A
JA
Besser
G M
GM
Clark
A J
AJ
D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D001120:Arginine; D001483:Base Sequence; D003062:Codon; D003545:Cysteine; D029721:Drosophila Proteins; D006801:Humans; D008969:Molecular Sequence Data; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010235:Paraganglioma / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
D003062:Codon; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D001120:Arginine; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; D003545:Cysteine