Dvorakova S, Vaclavikova E, Ryska A, Cap J, Vlcek P, Duskova J, Kodetova D, Holub V, Novak Z, Bendlova B
Institute of Endocrinology, Department of Endokrinology, Prague 1, Czech Republic.
Exp Clin Endocrinol Diabetes. 2006 Apr;114(4):192-6. doi: 10.1055/s-2006-924071.
Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.
甲状腺髓样癌（MTC）是一种罕见的甲状腺癌形式，约占所有甲状腺恶性肿瘤的10%。它大多表现为散发性肿瘤，或与常染色体显性遗传癌症综合征——2A和2B型多发性内分泌腺瘤病（MEN）以及家族性MTC相关。大多数家族性病例中可发现RET原癌基因第8、10、11、13、14、15和16外显子的种系突变。仅有少数已发表的数据报道了RET原癌基因中的多种种系突变。我们在两个MEN 2家族的同一RET等位基因的2个不同外显子中检测到了双种系突变。在MEN 2A家族中，检测到第10外显子（Cys620Phe）和第13外显子（Tyr791Phe）的双种系突变。在MEN 2B家族中，除了第16外显子（Met918Thr）的经典种系突变外，还在第13外显子中发现了第二个种系突变（Tyr791Phe）。本研究表明，MEN 2综合征也可由RET原癌基因中的双种系突变引起，这些家族可被纳入全球范围内具有多种种系突变的小家族队列中。
