分析RET protooncogene点突变遗传有别于nonheritable甲状腺髓样癌。
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Komminoth P Kunz EK Matias-Guiu X, Hiort O,克里斯琴森克,科罗姆,罗斯J, Heitz聚氨酯
分析RET protooncogene点突变遗传有别于nonheritable甲状腺髓样癌。
癌症。1995年8月1日,76 (3):479 - 89。
- PubMed ID
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8625130 (在PubMed]
- 文摘
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背景:零星的区别遗传性甲状腺髓样癌(mtc)是临床重要的预后的差异,和家族遗传咨询需要筛查的必要性在后者。在RET protooncogene的种系突变与多发性内分泌瘤(男性)2型,家族性甲状腺髓样癌(FMTC),和男性2型b。体细胞相同基因的点突变已确定在零星发生甲状腺髓样癌的一个子集。方法:nonisotopic聚合酶链反应(PCR)基于单链构象多态性(SSCP)分析和heteroduplex萃取DNA凝胶电泳法筛选32甲醛固定,石蜡包埋矿渣MTC标本和正常组织或血液的病人RET外显子点突变的10,11和16。点突变被发现nonisotopic循环使用一个自动化的dna测序仪的pcr产物测序。结果与疾病表型相比,临床发现,和随访。结果:六种不同的错义系突变被确定在618年半胱氨酸残基,630年和634年的cysteine-rich细胞外RET域编码外显子10和11 2 FMTC和男性患者。634密码子突变的频率高于男性患者2 634 FMTC和半胱氨酸- - >参数突变与甲状旁腺疾病三个病人。生殖系相遇——>刺点突变RET酪氨酸激酶域的密码子918患者被确认在所有三个男人2 b。两个临床零星的矿渣MTC和消极的家族史患者表现出后悔生殖系突变在634密码子,指示一个nonpredicted继承了矿渣MTC的存在。 Furthermore, one patient had a 618 Cys-->Ser mutation in the tumor and nontumorous thyroid DNA but not in blood DNA, indicating a mosaic mutation affecting thyroid tissue but not blood cells. Tumor specific (somatic) Met-->Thr point mutations at codon 918 were identified in 5 of 13 sporadic MTCs. The remaining eight sporadic MTCs lacked mutations in all three RET exons tested. CONCLUSIONS: This study demonstrates that (1) the molecular methods are not only suitable to identify asymptomatic individuals at risk for MEN 2A, FMTC, and MEN 2B but also to distinguish heritable from nonheritable MTCs using archival tissue specimens, and (2) that more MTCs than clinically expected are heritable, indicating the need for genetic analysis of all patients with MTC.