title: Frequent RET protooncogene mutations in multiple endocrine neoplasia type 2A.
abstract: The occurrence of mutations in the RET protooncogene has been investigated in 12 multiple endocrine neoplasia type 2A families and 18 cases of sporadic thyroid medullary carcinomas and pheochromocytomas. Ten of 12 families showed single base substitutions in the RET protooncogene exons 10 and 11, coding for the extracellular domain of the protein. Tumor tissues from 2 multiple endocrine neoplasia type 2A patients were analyzed at the DNA and ribonucleic acid levels and revealed the same heterozygous mutations found in the peripheral blood lymphocytes. This demonstrates that both the normal and mutant alleles are expressed. No mutations in these exons were detected in the 18 cases of sporadic tumors investigated. These data provided further evidence that the mutated RET protooncogene acts in a dominant fashion and is responsible for the pathogenesis of this syndrome.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, CEINGE, Centro di Ingegneria Genetica, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Quadro
authors.forename: L
authors.initials: L
authors.lastname: Panariello
authors.forename: D
authors.initials: D
authors.lastname: Salvatore
authors.forename: F
authors.initials: F
authors.lastname: Carlomagno
authors.forename: M
authors.initials: M
authors.lastname: Del Prete
authors.forename: V
authors.initials: V
authors.lastname: Nunziata
authors.forename: V
authors.initials: V
authors.lastname: Colantuoni
authors.forename: G
authors.initials: G
authors.lastname: Di Giovanni
authors.forename: M L
authors.initials: ML
authors.lastname: Brandi
authors.forename: M
authors.initials: M
authors.lastname: Mannelli
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000483:Alleles; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry; D029721:Drosophila Proteins; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000235:genetics*; D009154:Mutation; D010673:Pheochromocytoma / Q000235:genetics; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012334:RNA, Neoplasm / Q000032:analysis / Q000737:chemistry; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila