Faculty Collaboration Database

A novel point mutation of the RET protooncogene involving the second intracellular tyrosine kinase domain in a family with medullary thyroid carcinoma. J Clin Endocrinol Metab 2004 Jul;89(7):3521-6

Date

07/09/2004

Pubmed ID

15240641

DOI

10.1210/jc.2004-0073

Scopus ID

2-s2.0-3242729164 (requires institutional sign-in at Scopus site)   40 Citations

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.

Author List

Jimenez C, Dang GT, Schultz PN, El-Naggar A, Shapiro S, Barnes EA, Evans DB, Vassilopoulou-Sellin R, Gagel RF, Cote GJ, Hoff AO

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Arginine
Base Sequence
Carcinoma, Medullary
Female
Humans
Intracellular Membranes
Mutation, Missense
Pedigree
Point Mutation
Proline
Protein Structure, Tertiary
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-rel
Thyroid Neoplasms