Landsvater R M, Jansen R P, Hofstra R M, Buys C H, Lips C J, Ploos van Amstel H K
Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
Hum Genet. 1996 Jan;97(1):11-4. doi: 10.1007/BF00218825.
Hereditary C-cell carcinoma is encountered in multiple endocrine neoplasia type 2A (MEN 2A), MEN 2B, and familial medullary thyroid carcinoma (FMTC). Mutations of the RET proto-oncogene are associated with all three diseases. To obtain an insight into the molecular heterogeneity of MEN 2 syndromes and FMTC in the Netherlands, probands of 20 MEN 2A families, two FMTC families, and seven MEN 2B families were analyzed by the polymerase chain reaction (PCR), DNA sequencing, and restriction enzyme digestion for abnormalities in the RET proto-oncogene. RET mutations were found in all cases. All MEN 2A families had a mutation involving one of five cysteine codons in exons 10 and 11 of RET. Two novel dinucleotide mutations and a de novo mutation were found. Both FMTC families had a mutation of the Cys at codon 618. All MEN 2B probands carried a Met to Thr mutation in exon 16. All mutations could be confirmed by restriction enzyme digestion of PCR amplicons. Identification of the RET mutation in the Dutch population with hereditary C-cell carcinoma facilitates genetic testing for families or individuals at risk for MEN 2A, FMTC, and MEN 2B.
遗传性C细胞癌见于2A型多发性内分泌腺瘤病（MEN 2A）、MEN 2B和家族性甲状腺髓样癌（FMTC）。RET原癌基因的突变与所有这三种疾病相关。为深入了解荷兰MEN 2综合征和FMTC的分子异质性，对20个MEN 2A家系、2个FMTC家系和7个MEN 2B家系的先证者进行了聚合酶链反应（PCR）、DNA测序和限制性内切酶消化分析，以检测RET原癌基因的异常。所有病例均发现RET突变。所有MEN 2A家系均有涉及RET第10和11外显子中五个半胱氨酸密码子之一的突变。发现了两个新的二核苷酸突变和一个新发突变。两个FMTC家系均有第618密码子半胱氨酸的突变。所有MEN 2B先证者均携带第16外显子中由甲硫氨酸到苏氨酸的突变。所有突变均可通过对PCR扩增产物进行限制性内切酶消化来确认。在荷兰遗传性C细胞癌患者中鉴定RET突变有助于对有MEN 2A、FMTC和MEN 2B风险的家庭或个体进行基因检测。
