Molecular basis of medullary thyroid carcinoma: the role of RET polymorphisms.
Medullary thyroid carcinoma is a rare malignant tumor originating in parafollicular C cells. It accounts for 5 to 8% of all thyroid cancers. MTC develops in either sporadic (75%) or hereditary form (25%). Genetic and molecular studies have demonstrated the involvement of the RET proto-oncogene in hereditary MTC and, less often, in its sporadic form. Although a strong genotype-phenotype correlation has been described, wide clinical heterogeneity is observed among families with the same RET mutation or even in carriers of the same kindred. In recent years, several single nucleotide polymorphisms of the RET gene have been described in the general population as well as in patients with MTC. Some studies have reported associations between the presence of polymorphisms and development or progression of MTC. Nonetheless, other studies failed to demonstrate any effect of the RET variants. Differences in the genetic background of distinct populations or methodological approaches have been suggested as potential reasons for the conflicting results. Here, we review current knowledge concerning the molecular pathogenesis of sporadic and hereditary MTC. In particular, we analyze the role of RET polymorphisms in the clinical presentation and prognosis of MTC based on the current literature.
Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003, Porto Alegre, RS, Brazil; E-Mails:  lu.ceolin@gmail.com  (L.C.);  deborarsiqueira@yahoo.com.br  (D.R.S.);  mirianromitti@bol.com.br  (M.R.);  carlinhavaz@yahoo.com.br  (C.V.F.).
Lucieli
L
Ceolin
Débora R
DR
Siqueira
Mírian
M
Romitti
Carla V
CV
Ferreira
Ana Luiza
AL
Maia
D018278:Carcinoma, Neuroendocrine; D056726:Genetic Association Studies; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D020662:Guanine Nucleotide Exchange Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret