RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma

• Published in: Cancer Vol. 120; no. 13; pp. 1920 - 1931
• Main Authors: Krampitz, Geoffrey W., Norton, Jeffrey A.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.07.2014
• Subjects: Age Factors; Biological and medical sciences; calcitonin; Carcinoma, Medullary - congenital; Carcinoma, Medullary - diagnosis; Carcinoma, Medullary - genetics; Carcinoma, Medullary - prevention & control; DNA Mutational Analysis; Endocrinopathies; Evidence-Based Medicine; Family; General aspects. Associated endocrine diseases. Endocrine paraneoplasic syndromes; Genetic Counseling; Genetic Testing; Genotype; Germ-Line Mutation; Humans; Medical sciences; medullary thyroid cancer; Multiple Endocrine Neoplasia Type 2a - diagnosis; Multiple Endocrine Neoplasia Type 2a - drug therapy; Multiple Endocrine Neoplasia Type 2a - genetics; Multiple Endocrine Neoplasia Type 2a - prevention & control; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Phenotype; pheochromocytoma; Point Mutation; Precision Medicine; Primary Prevention - methods; Proto-Oncogene Proteins c-ret - genetics; RET; Risk Assessment; Thyroid Neoplasms - diagnosis; Thyroid Neoplasms - genetics; Thyroid Neoplasms - prevention & control; Thyroidectomy; Tumors; Endocrinopathy; RET; Pheochromocytoma; Typing; Thyroid diseases; Genotype; Thyroid medullary carcinoma; Malignant tumor; Genetic disease; Secretory tumor; Phenotype; Thyroid cancer; Cancerology; Multiple endocrine neoplasia; Calcitonin; C-Onc gene; medullary thyroid cancer; Thyroid hormone; Genetics; Mutation; Protooncogene; Cancer; pheochromocytoma; calcitonin
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28661

The rapid technical advances in molecular biology and accelerating improvements in genomic and proteomic diagnostics have led to increasingly personalized strategies for cancer therapy. Such an approach integrates the genomic, proteomic, and molecular information unique to the individual to provide an accurate genetic diagnosis, molecular risk assessment, informed family counseling, therapeutic profiling, and early preventative management that best fits the particular needs of each patient. The discovery of mutations in the RET proto‐oncogene resulting in variable onset and severity of multiple endocrine neoplasia type 2 (MEN2) was the first step in developing direct genetic testing for at‐risk individuals. Patients with germline RET mutations may undergo risk assessment and appropriate intervention based on specific mutations. Moreover, family members of affected individuals receive counseling based on understanding of the genetic transmission of the disease. Increasingly, clinicians are able to make therapeutic choices guided by an informative biomarker code. Improvements in detection and management of patients with MEN2 resulting from understanding of the RET proto‐oncogene are evidence of the benefits of personalized cancer medicine. This review describes the discovery of the RET proto‐oncogene, the association between genotype and phenotype, and the role of mutation analysis on diagnosis and treatment of MEN2. Cancer 2014;120:1920–1931. © 2014 American Cancer Society. MEN2 is a genetic syndrome caused by mutations in the RET proto‐oncogene with different penetrance producing 3 variants, MEN2A, MEN2B, and FMTC, each of which is characterized by MTC. The discovery of RET mutations that cause MEN2 lead to the development of genetic testing that enabled personalized approaches to diagnosis, risk stratification, and appropriate treatment.