title: A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A.
abstract: One hundred and eighty-one families with multiple endocrine neoplasia type 2A (MEN-2A) or familial medullary thyroid carcinoma (FMTC) have been investigated for mutations in the ret protooncogene in Germany. In 8 families with FMTC or MEN-2A, no mutation could be detected in the cysteine-rich domain encoded in exons 10 and 11 of the ret protooncogene. DNA sequencing of additional exons (no. 13-15) revealed rare noncysteine mutations in 3 families (codons 631, 768, and 844). In contrast to these rare events, heterozygous missense mutations in exon 13, codons 790 and 791, were found in 5 families (4 with MTC only; 1 family with MTC and pheochromocytoma) and 11 patients with apparently sporadic tumors. Two different mutations in codon 790 (TTG-->TTT, TTG-->TTC; Leu790Phe) and one mutation in codon 791 (TAT-->TTT; Tyr791Phe) created a phenylalanine residue. We conclude that codons 790 and 791 of the ret protooncogene represent a new hot spot for FMTC/MEN-2A causing mutations. With the discovery of these considerably common mutations in codons 790 and 791 and the identification of some rare mutations, 100% of the German FMTC/MEN-2A families could be characterized by a mutation in the ret protooncogene.
authors.affiliation: Institute for Hormone and Fertility Research, University of Hamburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Berndt
authors.forename: M
authors.initials: M
authors.lastname: Reuter
authors.forename: B
authors.initials: B
authors.lastname: Saller
authors.forename: K
authors.initials: K
authors.lastname: Frank-Raue
authors.forename: P
authors.initials: P
authors.lastname: Groth
authors.forename: M
authors.initials: M
authors.lastname: Grussendorf
authors.forename: F
authors.initials: F
authors.lastname: Raue
authors.forename: M M
authors.initials: MM
authors.lastname: Ritter
authors.forename: W
authors.initials: W
authors.lastname: Höppner
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila