Related Experiment Video
Updated: Apr 19, 2026
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr
Nuria Valdés1, Elena Navarro2, Jordi Mesa2
1Department of Endocrinology and NutritionHospital Universitario Central de Asturias, Avenida de Roma s/n, E-33011 Oviedo, Asturias, SpainDepartment of Endocrinology and NutritionHospital Universitario Virgen del Rocío, Sevilla, SpainDepartment of Endocrinology and NutritionHospital de Vall d'Hebron, Barcelona, SpainDepartment of Endocrinology and NutritionHospital Severo Ochoa, Madrid, SpainDepartment of Endocrinology and NutritionComplejo Hospitalario Universitario de Albacete, Albacete, SpainDepartment of Endocrinology and NutritionHospital Universitario Virgen de la Arrixaca, Murcia, SpainEndocrinology and Diabetes Research GroupDepartment of Endocrinology and NutritionHospital Universitario de Cruces, Barakaldo, SpainDepartment of EndocrinologyComplejo Hospitalario de Navarra, Pamplona, Spain nvaldes@hca.es.
Objective:
Specific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634.
Design:
The study was retrospective and multicentric.
Methods:
We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6±6.9 years (1-32).
Results:
Patients (n=173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P<0.001, P=0.007 and P<0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P<0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P<0.001).
Conclusions:
Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.
More Related Videos
09:34Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
09:33Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Related Concept Videos
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:23Abnormal Proliferation