title: [Detection of RET-proto-oncogene mutations in the diagnosis of Type 2 endocrine neoplasia (MEN 2)].
abstract: We have analyzed 95 blood- and 25 paraffin-derived DNA samples of 120 individuals from Switzerland (MEN 2 family members and patients with medullary thyroid carcinoma or pheochromocytoma) for the presence of RET protooncogene mutations in exons 10, 11, 13, 14 and 16, where recently germline point mutations have been identified in more than 95% of patients with MEN 2A, familial medullary thyroid carcinoma (FMTC) and MEN 2B. Molecular DNA screening of samples was performed by non-radioactive single strand conformation polymorphism (SSCP) and heteroduplex gel electrophoresis method followed by mutation analysis of PCR products by direct cycle sequencing using an automated DNA sequencer. We identified 12 MEN 2A/FMSC and 6 MEN 2B families with 29 gene carriers. Ten different types of mutations were identified in the MEN 2A/FMTC families (620 Cys-->Arg, 618 Cys-->Ser, Gly, 611 Cys-->Tyr; 634 Cys-->Arg, Tyr, Trp, Phe, Ser, Gly) and all 6 MEN 2B families had a 918 Met-->Thr point mutation. Our results indicate that PCR-based DNA testing for RET point mutations is a rapid, accurate and reproducible method of identifying MEN 2 gene carriers using blood or tissue DNA. Early detection of gene carriers allows preventive thyroidectomy without neck dissection or parathyroid transplantation, and non-gene carriers can be released from biochemical testing. Furthermore, it is shown that the distribution and localization of RET mutations in MEN 2 families from Switzerland concur with combined results of larger series and that a "founder effect" of MEN 2 can be excluded for this country.
authors.affiliation: Abteilung für Zell- und Molekularpathologie, Universitätsspital Zürich.
authors.forename: P
authors.initials: P
authors.lastname: Komminoth
authors.forename: S
authors.initials: S
authors.lastname: Muletta-Feurer
authors.forename: A
authors.initials: A
authors.lastname: Soltermann
authors.forename: E
authors.initials: E
authors.lastname: Gemsenjäger
authors.forename: H
authors.initials: H
authors.lastname: Bürgi
authors.forename: J J
authors.initials: JJ
authors.lastname: Staub
authors.forename: E
authors.initials: E
authors.lastname: Schönle
authors.forename: M
authors.initials: M
authors.lastname: Fried
authors.forename: W
authors.initials: W
authors.lastname: Vetter
authors.forename: G A
authors.initials: GA
authors.lastname: Spinas
authors.forename: P U
authors.initials: PU
authors.lastname: Heitz
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D029721:Drosophila Proteins; D006580:Genetic Carrier Screening; D006801:Humans; D008969:Molecular Sequence Data; D018813:Multiple Endocrine Neoplasia Type 2a / Q000175:diagnosis / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000302:isolation & purification*; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila
vernacular_title: Nachweis von RET-Proto-Onkogen-Mutationen zur Diagnostik der multiplen endokrinen Neoplasie Typ 2 (MEN 2).