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Schematic diagram of the RET protooncogene showing mutations found in MEN type 2 and sporadic medullary thyroid carcinoma (MTC). The RET protooncogene is located on the proximal arm of chromosome 10q (10q11.2). Activating mutations of two functional domains of RET tyrosine kinase receptor have been identified. The first affects a cysteine-rich (Cys-Rich) region in the extracellular portion of the receptor. Each germ-line mutation changes a cysteine at codons 609, 611, 618, 620, or 634 to another amino acid. The second region is the intracellular tyrosine kinase (TK) domain. Codon 634 mutations account for ∼80% of all germ-line mutations. Mutations of codons 630, 768, 883, and 918 have been identified as somatic (non-germ-line) mutations that occur in a single parafollicular or C cell within the thyroid gland in sporadic MTC. A codon 918 mutation is the most common somatic Source: Chapter 351. Disorders Affecting Multiple Endocrine Systems, Harrison's Principles of Internal Medicine, 18e mutation. MEN2, multiple endocrine neoplasia type 2; CLA, cutaneous lichen amyloidosis; FMTC, familial medullary thyroid carcinoma; Signal, the signal Citation: Longo DL, Fauci AS, DL, Hauser SL, Jameson J, Loscalzo J.domain; Harrison's of Internal Medicine, 18e; 2012 Available at: peptide; Cadherin, a cadherin-like region in Kasper the extracellular domain; TM, transmembrane TK,Principles tyrosine kinase domain. http://mhmedical.com/ Accessed: May 10, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved