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

Abstract

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;120:1920-31.

Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals

“…Gain-of-function mutations in RET cause multiple endocrine neoplasia (MEN) type 2 and FMTC [53]. On the contrary, loss-of-function mutations in RET are known to be risk factors for Hirschsprung disease (HSCR), which is caused by the congenital absence of parasympathetic ganglion cells in the intestinal tissues [54].…”

Genetic analysis and clinical investigation of a pedigree with multiple endocrine neoplasia type 2A: A case report

“…The symptoms of patients with MTC and C634R mutations are more severe compared with patients only diagnosed with MTC (7). Recently, the American Thyroid Association classified the risk levels of MEN2A, according to all recognized mutations and the aggressive nature of codon 634 (11). The patient in the present study had no evident nodules or neck nodes, or other characteristic manifestations of MTC at the first visit to the hospital.…”

Neoplasia endocrina múltiple tipo IIa (síndrome de Sipple) de diagnóstico incidental con feocromocitoma bilateral y carcinoma medular de tiroides. Reporte de un caso

“…La tiroidectomía profiláctica es el único tratamiento curativo, estando supeditada al tipo de mutación 25,26 . Dado que la concordancia entre la presencia de la enfermedad y el estado del portador de la mutación es de más del 95%, el estudio debe ser realizado también a los familiares consanguíneos.…”