[Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit]
Marcelo A C G dos Santos1, Adriana Bezerra Nunes, Neusa Abelin
1Unidade de Endocrinologia Genética, Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, SP.
Abstract:
Multiple endocrine neoplasia type 2 (MEN-2) is an inherited tumor syndrome that includes medullary thyroid carcinoma (MTC), primary hyperparathyroidism, pheochromocytoma and other non-endocrine diseases. Since the first RET missense mutations in association with MEN-2 were identified, RET mutation analysis had a great impact in the clinical management of MEN-2, such as in early diagnosis and treatment of MTC. Presently, early total thyroidectomy provides real cure of MTC for cases in which molecular diagnosis has been performed at early ages. After RET mutation identification, family members should be screened for this mutation by using methods as DGGE, SSCP, restriction enzyme, genetic sequencing or mini-sequencing. In this paper, we briefly review our experience with the direct RET gene sequencing and DGGE approaches. In 50 typical MEN-2 patients analyzed using both methods, we found no false results suggesting that DGGE is a reliable screening method for RET proto-oncogene mutation analysis.
Insights
Genetic testing for RET proto-oncogene mutations aids in early diagnosis and treatment of Multiple Endocrine Neoplasia type 2 (MEN-2). Denaturing Gradient Gel Electrophoresis (DGGE) is a reliable screening method for these RET mutations.
Area of Science:
- Genetics
- Oncology
- Endocrinology
Background:
- Multiple Endocrine Neoplasia type 2 (MEN-2) is an inherited cancer syndrome.
- RET proto-oncogene mutations are key drivers of MEN-2, leading to medullary thyroid carcinoma (MTC) and other tumors.
- Early diagnosis and intervention, such as thyroidectomy, significantly improve patient outcomes.
Purpose of the Study:
- To evaluate the reliability of Denaturing Gradient Gel Electrophoresis (DGGE) as a screening method for RET proto-oncogene mutations in MEN-2 patients.
- To compare DGGE with direct RET gene sequencing for mutation detection.
Main Methods:
- Analysis of 50 MEN-2 patients using both direct RET gene sequencing and DGGE.
- Review of clinical management strategies impacted by RET mutation identification.
Main Results:
- Both DGGE and direct RET gene sequencing were employed for mutation analysis.
- No false results were observed when using DGGE, indicating its accuracy.
- DGGE proved to be a dependable method for screening RET proto-oncogene mutations.
Conclusions:
- RET mutation analysis is crucial for the early diagnosis and management of MEN-2, particularly MTC.
- DGGE is a reliable and effective screening tool for identifying RET proto-oncogene mutations in MEN-2 patients.
- Early molecular diagnosis enables timely interventions like total thyroidectomy, offering a cure for MTC.
