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[The molecular pathology of RET protooncogene in families with multiple endocrine neoplasia type 2A]
J Biarnés1, M Miranda, J Corral
1Departamento de Genética Molecular, L'Hospitalet de Liobregat, Barcelona.
Background:
Multiple endocrine neoplasm type 2A (MEN 2A) is an autosomal dominantly inherited disease characterized by medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. Mutations have been identified in the extracellular domain of the RET proto-oncogen product (10q11.2) in MEN 2A patients. In each case a single base pair substitution results in replacement of cysteine with another amino acid. Most MEN 2A patients have mutations of codon 634.
Patients And Methods:
Sixty-five unrelated MEN 2A patients from seven families were studied. Polymerase chain reaction, segregation, sequence analysis and restriction enzyme digestion were performed.
Results:
Of seven families, four had the TGC to TAC transition, two families the TGC to TGG transversion and one family the TGC to CGC transition in codon 634 of RET.
Conclusions:
We found all the mutations in codon 634. The characterization of MEN 2A mutations allows early and presymptomatic diagnosis in this syndrome.
Insights
Multiple endocrine neoplasia type 2A (MEN 2A) is linked to RET proto-oncogene mutations at codon 634. Identifying these specific RET mutations enables early diagnosis and presymptomatic screening for MEN 2A.
Area of Science:
- Genetics
- Oncology
- Endocrinology
Background:
- Multiple endocrine neoplasia type 2A (MEN 2A) is an inherited disorder.
- MEN 2A is characterized by medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism.
- RET proto-oncogene mutations are implicated in MEN 2A, often involving codon 634.
Purpose of the Study:
- To investigate the specific mutations within codon 634 of the RET proto-oncogene in MEN 2A patients.
- To characterize the genetic basis of MEN 2A in affected families.
Main Methods:
- Studied 65 unrelated MEN 2A patients from seven families.
- Employed polymerase chain reaction, segregation analysis, sequence analysis, and restriction enzyme digestion.
Main Results:
- All investigated mutations were located in codon 634 of the RET gene.
- Identified specific base pair substitutions: TGC to TAC (4 families), TGC to TGG (2 families), and TGC to CGC (1 family).
Conclusions:
- Confirmed that all MEN 2A mutations in this cohort occurred at codon 634 of the RET gene.
- Characterization of these mutations facilitates early and presymptomatic diagnosis of MEN 2A.