Hereditary Medullary Thyroid Cancer: Genotype-Phenotype Correlation.

Q3 Medicine
Karin Frank-Raue, Friedhelm Raue
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引用次数: 0

Abstract

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant hereditary cancer syndrome caused by germline variants in the REarranged during Transfection (RET) proto-oncogene. MEN2 is caused by autosomal dominant gain-of-function mutations in the RET proto-oncogene. There are two clinically distinct types of MEN2 syndrome, termed MEN2A and MEN2B. MEN2A is associated with medullary thyroid carcinoma (MTC) and the less frequent occurrence of pheochromocytoma, primary hyperparathyroidism, or both, rarely with cutaneous lichen amyloidosis or Hirschsprung's disease. MEN2B is associated with MTC, pheochromocytoma, and other noncancerous abnormalities, such as Marfanoid habitus and ganglioneuromas of the intestines. Specific RET mutations suggest a predilection toward a particular phenotype and clinical course with strong genotype-phenotype correlation. Based upon these genotype-phenotype correlations, RET mutations are stratified into three risk levels, i.e., highest, high, and moderate risk, based on the age of onset and the penetrance of the MTC. Children in the highest risk category develop MTC within the first year of life and should undergo thyroidectomy in their first year, perhaps even in their first months of life. In children in the high-risk category, ultrasound of the neck and calcitonin (Ctn) measurement should be performed prior to thyroidectomy. Thyroidectomy should typically be performed at 5 years of age or earlier, depending on the presence of elevated serum Ctn levels. However, heterogeneity in disease expression and progression within these groups varies considerably. To personalize disease management, the decision regarding the age of prophylactic thyroidectomy is no longer based upon genotype alone but is currently driven by additional clinical data, the most important being serum Ctn levels. In the moderate-risk group, the timing of thyroidectomy is particularly dependent on the Ctn level. Personalized management also includes decisions about the best age to begin biochemical screening for pheochromocytoma and primary hyperparathyroidism.

遗传性甲状腺髓样癌:基因型-表型相关性。
多发性内分泌肿瘤2型(MEN2)是一种常染色体显性遗传性癌症综合征,由RET原癌基因重排时的种系变异引起。MEN2是由RET原癌基因的常染色体显性功能获得突变引起的。临床上有两种不同类型的MEN2综合征,称为MEN2A和MEN2B。MEN2A与甲状腺髓样癌(MTC)以及嗜铬细胞瘤、原发性甲状旁腺功能亢进症或两者的发生率较低相关,很少与皮肤苔藓淀粉样变或Hirschsprung病相关。MEN2B与MTC、嗜铬细胞瘤和其他非癌性异常有关,如肠的类麻氏瘤和神经节神经瘤。特定的RET突变表明对特定表型和临床过程的偏好具有很强的基因型-表型相关性。基于这些基因型-表型相关性,根据发病年龄和MTC的外显率,将RET突变分为三个风险水平,即最高、高和中等风险。风险最高的儿童在出生后的第一年就会患上MTC,应该在出生后的第一年,甚至出生后的头几个月接受甲状腺切除术。对于高危儿童,应在甲状腺切除术前进行颈部超声检查和降钙素(Ctn)测定。甲状腺切除术通常应在5岁或更早进行,这取决于血清Ctn水平升高的存在。然而,这些组中疾病表达和进展的异质性差异很大。为了个性化疾病管理,关于预防性甲状腺切除术年龄的决定不再仅仅基于基因型,而是目前由额外的临床数据驱动,最重要的是血清Ctn水平。在中度风险组中,甲状腺切除术的时机特别依赖于Ctn水平。个性化管理还包括决定开始嗜铬细胞瘤和原发性甲状旁腺功能亢进生化筛查的最佳年龄。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
5.60
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