title: A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene.
abstract: We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche e Ceinge, Centro di Ingegneria Genetica, Università degli Studi di Napoli Federico II, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tessitore
authors.forename: A A
authors.initials: AA
authors.lastname: Sinisi
authors.forename: D
authors.initials: D
authors.lastname: Pasquali
authors.forename: M
authors.initials: M
authors.lastname: Cardone
authors.forename: D
authors.initials: D
authors.lastname: Vitale
authors.forename: A
authors.initials: A
authors.lastname: Bellastella
authors.forename: V
authors.initials: V
authors.lastname: Colantuoni
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution; D001483:Base Sequence / Q000235:genetics; D002116:Calcitonin / Q000378:metabolism; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila