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RET is expressed but not mutated in extra‐adrenal paragangliomas
Author(s) -
Krijger Ronald R. de,
Harst Erwin van der,
MulettaFeurer Seraina,
Bruining Hajo A.,
Lamberts Steven W. J.,
Dinjens Winand N. M.,
Roth Jürgen,
Heitz Philipp U.,
Komminoth Paul
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(2000)9999:9999<::aid-path638>3.0.co;2-i
Subject(s) - ret proto oncogene , exon , heteroduplex , point mutation , multiple endocrine neoplasia type 2 , pheochromocytoma , biology , paraganglioma , single strand conformation polymorphism , proto oncogene proteins c ret , oncogene , immunohistochemistry , germline mutation , gene , microbiology and biotechnology , cancer research , mutation , genetics , pathology , medicine , endocrinology , immunology , receptor , cell cycle , neurotrophic factors , glial cell line derived neurotrophic factor
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. Copyright © 2000 John Wiley & Sons, Ltd.