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Updated: Dec 18, 2025
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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
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A Novel Double RET E768D/L790F Mutation Associated with a MEN2B-Like Phenotype
Annie Mathew1, Soeren Latteyer1, Karin Frank-Raue2
1Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Summary
A novel double RET mutation, E768D/L790F, was identified in a patient with MEN2B-like features. This mutation drives aggressive medullary thyroid carcinoma (MTC) and pheochromocytoma, similar to known MEN2B mutations.
Area of Science:
- Genetics
- Oncology
- Endocrinology
Background:
- Multiple Endocrine Neoplasia type 2 (MEN2) is a genetic disorder caused by RET proto-oncogene mutations.
- MEN2B is a subtype characterized by aggressive medullary thyroid carcinoma (MTC), pheochromocytoma, and distinct physical features.
Observation:
- A 39-year-old male presented with early-onset metastatic MTC and MEN2B-like physical features.
- Family history revealed MTC and pheochromocytoma in his mother and maternal uncle.
- RET sequencing identified a novel germline mutation, E768D/L790F, in the patient and his mother.
Findings:
- The novel double RET E768D/L790F mutant demonstrated increased ligand-independent RET phosphorylation.
- This mutation activated the MAPK pathway and promoted cell colony formation.
- Functional analysis showed the double mutant mimicked the transforming capacity of the known MEN2B RET M918T mutation.
Implications:
- Identifies a new RET mutation associated with MEN2B phenotype.
- Provides insights into the molecular mechanisms of aggressive MTC.
- Highlights the importance of genetic testing for RET mutations in MEN2 patients.
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