Información del artículo
El carcinoma medular de tiroides (CMT) puede presentarse en forma esporádica o familiar, en cuyo caso se integra en la neoplasia endocrina múltiple tipo 2 (NEM 2). La NEM 2 se origina como consecuencia de mutaciones germinales en el gen RET. Este gen incluye 21 exones y codifica el receptor RET, un receptor de membrana citoplasmática con actividad tirosinacinasa. La peculiaridad de esta alteración reside en la posibilidad de establecer una relación genotipo-fenotipo. Las distintas mutaciones en los codones del gen RET dan lugar a diversos cuadros clínicos, etiquetados clásicamente como NEM 2A, NEM 2B y CMTF (CMT familiar). En los últimos años se ha añadido una nueva clasificación en función de la agresividad del comportamiento tumoral, en la que se distinguen 3 niveles de riesgo. En la presente revisión exponemos las características fisiológicas y patológicas del gen RET, la relación genotipo-fenotipo tanto clásica como por grados de agresividad, los elementos posiblemente modificadores en esa relación (polimorfismos de un único nucleótido), la actitud a adoptar ante el CMT y el tratamiento recomendado según las características genéticas.
Palabras clave:
Carcinoma medular de tiroides
Neoplasia endocrina múltiple tipo 2 (NEM 2) Gen RET
Relación genotipo-fenotipo
Medullary thyroid carcinoma (MTC) can be sporadic or hereditary. The hereditary form of MTC is classified as multiple endocrine neoplasia type 2 (MEN 2). MEN 2 syndromes are caused by germinal mutations in the RET proto-oncogene. The RET gene includes 21 exons and encodes a plasma membrane-bound tyrosine kinase enzyme, the RET receptor. The peculiarity of this disease lies in the possibility of establishing genotype-phenotype correlations.
Distinct RET codon mutations give rise to the different MEN 2 syndromes, traditionally classified as MEN 2A, MEN 2B and familial MTC. In the last few years, a new classification has been suggested, based on biologic tumoral aggressiveness, in which RET mutations are stratified into three levels of risk.
In this review, we explain the physiological and pathological features of the RET gene, genotype-phenotype correlations (both traditional and the new risk classification), the elements that may modify this relationship (such as single nucleotide polymorphisms), suggested clinical decision-making in MTC and genetically-based treatment.
Key words:
Medullary thyroid carcinoma
MEN 2A (multiple endocrine neoplasia type 2)
RET gene
Genotype-phenotype correlation
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