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[Somatic ret proto-oncogene mutations in sporadic C-cell carcinoma of the thyroid gland]
A Frilling1, M Bockhorn, V Kalinin
1Abteilung für Allgemeinchirurgie, Universitäts-Krankenhaus Hamburg-Eppendorf.
Abstract:
Germline mutations of the RET proto-oncogene localized on chromosome 10q11.2 are the underlying cause of hereditary medullary thyroid carcinoma. In MEN 2A and FMTC, mutations can be found in exons 10, 11, 13 or 14. MEN 2B is characterized by a specific mutation in exon 16. In a significant number of sporadic MTC somatic mutations in codon 918 (exon 16) are detectable. Some rare sporadic MTC present somatic mutations in codons 611, 634, 768 and 883. Recently, deletion-insertion of the RET proto-oncogene in exon 11 and a deletion in exon 10 has been found. RET proto-oncogene mutations are not only responsible for the development of the familial MTC, but may also play an important role in the pathogenesis of sporadic MTC. However, the prognostic relevance of these somatic events is still unclear.
Insights
Germline mutations in the RET proto-oncogene cause hereditary medullary thyroid carcinoma (MTC). Somatic mutations also contribute to sporadic MTC, but their prognostic significance remains unclear.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations in the RET proto-oncogene.
- Specific RET mutations are associated with Multiple Endocrine Neoplasia type 2A (MEN 2A), Familial Medullary Thyroid Carcinoma (FMTC), and MEN 2B.
Purpose of the Study:
- To investigate the role of RET proto-oncogene mutations in both hereditary and sporadic medullary thyroid carcinoma.
- To explore the spectrum of RET mutations and their locations within the gene.
Main Methods:
- Analysis of germline and somatic mutations in the RET proto-oncogene.
- Identification of mutations in specific exons (10, 11, 13, 14, 16) and codons (e.g., 918, 611, 634).
Main Results:
- Germline RET mutations in exons 10, 11, 13, or 14 are found in MEN 2A and FMTC.
- A specific mutation in exon 16 characterizes MEN 2B.
- Somatic mutations, particularly in codon 918 (exon 16), are frequent in sporadic MTC, with rarer mutations in other codons.
- Novel deletions and insertion-mutations in RET exon 11 and deletions in exon 10 were recently identified.
Conclusions:
- RET proto-oncogene mutations are crucial in the development of familial MTC and play a significant role in sporadic MTC pathogenesis.
- The prognostic implications of somatic RET mutations in MTC require further investigation.