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Mutation of the RET protooncogene in sporadic medullary thyroid carcinoma
Author(s) -
Eng Charis,
Mulligan Lois M.,
Smith Darrin P.,
Healey Catherine S.,
Frilling Andrea,
Raue Friedhelm,
Neumann Hartmut P. H.,
Pfragner Roswitha,
Behmel Annemarie,
Lorenzo Maria J.,
Stonehouse Timothy J.,
Ponder Margaret A.,
Ponder Bruce A. J.
Publication year - 1995
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.2870120308
Subject(s) - exon , germline mutation , multiple endocrine neoplasia type 2 , missense mutation , mutation , germline , cancer research , thyroid carcinoma , genetics , multiple endocrine neoplasia , biology , proto oncogene proteins c ret , cancer syndrome , medicine , thyroid , gene , receptor , neurotrophic factors , glial cell line derived neurotrophic factor
Medullary thyroid carcinoma (MTC) occurs sporadically or as part of the inherited cancer syndrome multiple endocrine neoplasia (MEN) type 2. In MEN 2A, germline missense mutations are found in one of five cysteine codons within exons 10 and 11 in the extracellular domain of the RET protooncogene. In MEN 2B, germline mutations occur in codon 918 (exon 16) within the catalytic core of the tyrosine kinase domain. To determine if RET mutations similar to those in MEN 2A and 2B play a role in the pathogenesis of sporadic MTC, we analysed 71 sporadic tumours comprising 68 primary tumours and three cell lines, for mutations in RET exons 10, 11, and 16. We found that 23% of sporadic MTC had RET codon 918 mutations, while only 3% had exon 10 mutations, and none had mutations in exon 11. We found no exon 16 mutations in MTC from 14 MEN 2A cases. Thus, exon 10 and 11 mutations, commonly found in familial MTC and MEN 2A, rarely occur in sporadic MTC; somatic mutation of RET codon 918 appears to play a role in the tumourigenesis of a significant minority of sporadic MTC but not MEN 2A tumours. In addition to their biological interest, these findings may have some clinical application in determining whether a patient presenting with isolated MTC is truly sporadic or is part of an inherited cancer syndrome.