A patient with MEN 2 and multiple mutations of RET in the germline.
A patient with MEN 2 and multiple mutations of RET in the germline.
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一名患有 MEN 2 且种系存在 RET 多重突变的患者。
DOI：
10.1055/s-2000-11001
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Pacak,K
中科院分区：
文献类型：
--
作者：
Koch,CA;Huang,SC;Vortmeyer,AO;Zhuang,Z;Chrousos,GP;Pacak,K
We read with interest the article by Bartsch et al.(2000) on a RET double mutation in the germline of a family with multiple endocrine neoplasia type 2 (MEN 2). Although mutations of the RET protooncogene are responsible for the development of MEN 2-associated tumors, the mechanism (s) explaining why only few of the affected cells in the target organs develop into tumors, are unknown (Ponder, 1999). Interestingly, recently described RET double mutations in the germline of patients with MEN 2 did not correlate with a more aggressive phenotype, although these double mutations affected functional domains of RET, in the case described by Bartsch et al.(2000) the cysteine-rich domain of exon 11, and in another case the tyrosine kinase domain of exon 14 (Tessitore et al., 1999). Importantly, in both of these cases, the double mutations of RET occurred on the same RET allele with one allele still remaining wildtype RET. Wild-type RET may exert a protective/neutralizing effect and may thereby compensate for the activating effects of the mutant RET allele. We would like to report a patient with MEN 2A, in whom we found 3 germline mutations of RET. A 40-year-old Caucasian woman presented with a neck mass that was diagnosed as metastatic medullary thyroid cancer. Biochemical screening for catecholamines revealed that the patient also had pheochromocytoma. She underwent thyroidectomy with radical neck dissection and bilateral adrenalectomy. On 3 year follow-up, she has no evidence of (recurrent) pheochromocytoma but of metastatic thyroid cancer with plasma calcitonin levels around 400 pg/ml (normal,< 14). Mutation analysis of geonomic blood DNA for RETrevealed an exon 11 mutation (codon 631 GAC/TAC) in association with two new mutations of exon 14 (codon 819 AGC/ATC, codon 843 GAG/GAT)(Fig. 1), both in functional domains of RET. In patients with MEN 2, the biological significance of more than one RET mutation needs to be further elucidated.
