The discovery of the ret proto-oncogene in 1993 demonstrates the influence of genetic testing on clinical
practice. A germline mutation in the RET gene, which is located on chromosome 10,
leads to an alteration of the transmembrane tyrosine kinase receptor, which is expressed
primarily in neuroendocrine and neural cells. A patient with this genotype phenotypically
can express several disease states that include medullary thyroid cancer (MTC), hyperparathyroidism,
pheochromocytoma, and, less commonly, Hirschsprung's disease and cutaneous lichen
amyloidosis. The expression of “inheritable” MTC occurs in the context of multiple
endocrine neoplasia (MEN) II A, MEN II B, and familial MTC. The eventual neoplastic
transformation of normal thyroid parafollicular C-cells to C-cell hyperplasia (CCH),
and MTC occurs with 100% penetrance in patients with a germline mutation in the RET
gene. This definitive pattern of expression should allow for prophylactic surgical
intervention before the formation of MTC. The issue is when to perform thyroidectomy
in patients with this tumor, because the procedure is technically more demanding and
prone to complications the younger the patient, but the risk of tumor transformation
or dissemination increases while waiting.
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References
- Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations.Surgery. 2003; 134: 425-431
- Multiple endocrine neoplasia type 2: evaluation of the genotype-phenotype relationship.Arch Surg. 2003; 138: 409-416
- The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2: international RET mutation consortium analysis.JAMA. 1996; 276: 1575-1579
Article info
Publication history
Accepted:
June 17,
2003
Identification
Copyright
© 2004 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
