title: A novel point mutation of the RET protooncogene involving the second intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.
abstract: Hereditary medullary thyroid carcinoma, a tumor that arises from the parafollicular cells of the thyroid gland, occurs in isolation (as in familial medullary thyroid carcinoma), in association with hyperparathyroidism and pheochromocytoma (as in multiple endocrine neoplasia type 2A), or in association with pheochromocytoma, marfanoid habitus, and mucosal neuromas (as in multiple endocrine neoplasia type 2B). These genetic syndromes are associated with germline-activating mutations of the RET protooncogene, a cell surface tyrosine kinase receptor, which is believed to modulate specific intracellular signaling pathways involved in the regulation of C cell proliferation and apoptosis. RET-activating mutations involve two important functional areas of the receptor: the cysteine-rich extracellular domain and the intracellular tyrosine kinase domain. Multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma are more commonly associated with mutations in the cysteine-rich extracellular domain, whereas multiple endocrine neoplasia type 2B is exclusively associated with mutations involving the second intracellular tyrosine kinase domain. Here, we describe a novel missense mutation of the RET protooncogene that substitutes arginine for proline at codon 912 of the intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma.
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 435, Houston, TX 77030, USA.
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Dang
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Schultz
authors.forename: Adel
authors.initials: A
authors.lastname: El-Naggar
authors.forename: Suzanne
authors.initials: S
authors.lastname: Shapiro
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Barnes
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Evans
authors.forename: Rena
authors.initials: R
authors.lastname: Vassilopoulou-Sellin
authors.forename: Robert F
authors.initials: RF
authors.lastname: Gagel
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.forename: Ana O
authors.initials: AO
authors.lastname: Hoff
mesh_terms: D000293:Adolescent; D001120:Arginine; D001483:Base Sequence; D018276:Carcinoma, Medullary / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology*; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D011392:Proline; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D020569:Proto-Oncogene Proteins c-rel; D001120:Arginine; D011392:Proline; D011505:Protein-Tyrosine Kinases