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Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas
C Scurini1, L Quadro, O Fattoruso
1Istituto di Endocrinologia, Facoltà di Medicina, Seconda Università di Napoli, Italy.
Abstract:
Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.
Insights
Genetic analysis of RET proto-oncogene mutations in 50 medullary thyroid carcinoma (MTC) patients revealed germline mutations in three cases, indicating familial MTC. Somatic mutations were found in 30% of patients, suggesting sporadic MTC.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- Medullary thyroid carcinoma (MTC) can be sporadic or familial, linked to multiple endocrine neoplasia (MEN) type 2 syndromes.
- Accurate diagnosis is crucial as familial and sporadic MTC require different clinical management strategies.
- The RET proto-oncogene is frequently implicated in MTC development.
Purpose of the Study:
- To identify germline and somatic RET proto-oncogene mutations in patients clinically diagnosed with sporadic MTC.
- To differentiate between familial and sporadic MTC cases for appropriate patient and family management.
- To determine the frequency of RET mutations in a cohort of MTC patients.
Main Methods:
- Analysis of RET proto-oncogene mutations in 50 patients diagnosed with sporadic MTC.
- Sequencing of specific exons (11, 14, and 16) of the RET gene.
- Correlation of mutation status with clinical diagnosis and family history.
Main Results:
- Germline RET mutations were identified in three patients (6%), confirming familial MTC.
- Somatic RET mutations were detected in eight patients (30%), consistent with sporadic MTC.
- Specific mutations included exon 11 and 14 alterations for germline, and codon 918 (exon 16) or codon 634 (exon 11) for somatic mutations.
Conclusions:
- Genetic testing for RET mutations can distinguish familial from sporadic MTC in clinically diagnosed sporadic cases.
- Identification of germline mutations necessitates evaluation of family members.
- A tailored genetic and clinical management approach is recommended based on MTC inheritance patterns.