Genotype-phenotype correlation in multiple endocrine neoplasia type 2

Abstract

Multiple endocrine neoplasia type 2 is an autosomal-dominant hereditary cancer syndrome caused by missense gain-of-function mutations of the rearranged during transfection proto-oncogene, which encodes the receptor tyrosine kinase, on chromosome 10. It has a strong penetrance of medullary thyroid carcinomas and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Multiple endocrine neoplasia type 2 is divided into three varieties depending on its clinical features: multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, and familial medullary thyroid carcinoma. The specific rearranged during transfection mutation may suggest a predilection toward a particular phenotype and clinical course of medullary thyroid carcinoma, with strong genotype-phenotype correlations. Offering rearranged during transfection testing is the best practice for the clinical management of patients at risk of developing multiple endocrine neoplasia type 2, and multiple endocrine neoplasia type 2 has become a classic model for the integration of molecular medicine into patient care. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on the classification of rearranged during transfection mutations into risk levels according to genotype-phenotype correlations. Earlier identification of patients with hereditary medullary thyroid carcinoma can change the presentation from clinical tumor to preclinical disease, resulting in a high cure rate of affected patients and a much better prognoses.

Genetic screening of patients with medullary thyroid cancer in a referral center in Greece during the past two decades

“…1, D1). HIRSC in the context of MEN2A syndrome has invariably been associated with exon 10 mutations, which is in agreement with our results (27). Interestingly, 7.5% of exon 10 Figure 2 One large kindred followed in our center for four generations.…”

Multiple Endocrine Neoplasia Type 2A Patient with Metastatic Medullary Thyroid Carcinoma and Unilateral Multicentric Pheochromocytoma: A Case Report and Literature Review

“…More indolent MEN2B is associated with RET mutation at codon 883 [22,23]. MEN2 patients are stratified for risk based upon the RET mutation, and genotype-phenotype correlation exists [24]. The highest risk mutation is RET M819T, which is associated with MEN2B and causes aggressive MTC at a young age.…”

A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma

“…Pheo is defined as a tumor arising from catecholamine-producing chromaffin cells in the adrenal tion may be responsible for a particular phenotype (average age of onset, penetrance, clinical features and a more or less aggressive clinical course) [8].…”

“…About 98% of patients with MEN 2 have germline mutations in exons 5,8,10,11,13,14,15 or 16 of the RET gene. The most frequent RET mutation in MEN 2 syndrome is located in exon 11 at codon 634.…”