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Mutational analysis of the RET proto-oncogene in 71 Japanese patients with medullary thyroid carcinoma.
Journal of Human Genetics ( IF 3.5 ) Pub Date : 1998-06-11 , DOI: 10.1007/s100380050048
S Shirahama 1 , K Ogura , H Takami , K Ito , T Tohsen , A Miyauchi , Y Nakamura
Affiliation  

Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinomas (FMTC) are caused by germline mutations in the RET proto-oncogene. To investigate the spectrum of RET mutations among Japanese patients, we screened the RET gene in 71 patients with thyroid carcinomas. The panel included representatives of 44 families carrying FMTC or MEN2, 22 sporadic medullary thyroid carcinomas (MTCs), and five MTCs without familial information. Mutations in nucleotide sequences encoding one of three specific cysteine residues in the extracellular domain of the RET protein were found in 33 of the 34 MEN2A patients and in five of the six FMTC patients examined. A mutation at codon 918, causing the substitution of threonine for methionine in the tyrosine kinase domain of the protein, was found in germline DNAs of all four patients with MEN2B and in two of the 22 patients with sporadic MTCs; codon 918 was mutated somatically in tumor DNAs from three other sporadic cases. Germline mutations of codon 768, GAG to GAC (Glu to Asp), were detected in one FMTC, in one patient with sporadic MTC, and in one of the patients without familial information. Two somatic mutations, an Asp to Gly substitution at codon 631 and a Cys to Arg substitution at codon 634, had not been reported previously. Of five germline mutations found among the 22 sporadic cases, four were confirmed as de novo mutations since in each case neither parent carried the mutation. As nearly one-fourth of the patients with sporadic MTCs carried germline mutations and 50% of their children are expected to develop MTC and other endocrine tumors, these results indicated the importance of careful clinical surveillance of family members of any patient with MTC.

中文翻译:

甲状腺甲状腺髓样癌中RET原癌基因的突变分析(71例)。

多发性内分泌肿瘤2A和2B型(MEN2A和MEN2B)和家族性甲状腺髓样癌(FMTC)是由RET原癌基因中的种系突变引起的。为了调查日本患者中RET突变的频谱,我们在71例甲状腺癌患者中筛选了RET基因。小组成员包括44个携带FMTC或MEN2的家庭,22个散发性甲状腺髓样癌(MTC)和5个没有家族信息的MTC的代表。在34位MEN2A患者中,有33位在FMTC患者中有5位在RET蛋白的胞外域中,发现了编码三个特定半胱氨酸残基之一的核苷酸序列中的突变。918号密码子处的突变,导致该蛋白质的酪氨酸激酶结构域中的苏氨酸被蛋氨酸取代,在所有4例MEN2B患者和22例散发MTC患者中,有2例在种系DNA中被发现。918个密码子在其他三个零星病例的肿瘤DNA中进行了体细胞突变。在一名FMTC,一名散发MTC的患者和一名无家族信息的患者中检测到768个密码子的种系突变,GAG为GAC(Glu为Asp)。之前尚未报道过两个体细胞突变,第631位密码子由Asp取代Gly,第634位密码子由Cys取代Arg。在22例散发病例中发现的5个种系突变中,有4个被确认为从头突变,因为在每种情况下,父母双方均未携带该突变。由于近四分之一的散发性MTC患者携带种系突变,预计他们的孩子中有50%会发展出MTC和其他内分泌肿瘤,
更新日期:2019-11-01
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