Microsatellite mutation (CAG24-->18) in the androgen receptor gene in human prostate cancer.
Microsatellite mutation (CAG24-->18) in the androgen receptor gene in human prostate cancer.
复制标题
人类前列腺癌雄激素受体基因中的微卫星突变（CAG24-->18）。
DOI：
10.1006/bbrc.1994.1011
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发表时间：
1994
影响因子：
3.1
通讯作者：
Barrack,ER
中科院分区：
文献类型：
--
作者：
Schoenberg,MP;Hakimi,JM;Wang,S;Bova,GS;Epstein,JI;Fischbeck,KH;Isaacs,WB;Walsh,PC;Barrack,ER
雄激素受体 (AR) 基因包含一个多态性 CAG 微卫星，编码 AR 蛋白中可变长度的谷氨酰胺重复序列。微卫星 DNA 序列可能是遗传不稳定的潜在位点。 Using the polymerase chain reaction (PCR), we screened 40 human prostate cancer specimens for expansions or deletions of this microsatellite.在一名患者中，非肿瘤 DNA 产生了单一 PCR 产物，正如 AR 所预期的那样，但肿瘤 DNA 产生了两种不同的产物，一种与正常相同，另一种较小。直接测序显示，非肿瘤组织包含 24 个 CAG，而肿瘤组织包含一个包含 24 个 CAG 的片段（野生型）和第二个包含 18 个 CAG 的片段（突变型），代表肿瘤中 AR CAG 重复序列（CAG24→CAG18）的体细胞收缩。有趣的是，该患者对抗雄激素氟他胺的激素治疗表现出矛盾的激动反应。
The androgen receptor (AR) gene contains a polymorphic CAG microsatellite that codes for a variable length of glutamine repeats in the AR protein. Microsatellite DNA sequences may be potential sites of genetic instability. Using the polymerase chain reaction (PCR), we screened 40 human prostate cancer specimens for expansions or deletions of this microsatellite. In one patient, nontumor DNA yielded a single PCR product, as expected for the AR, but the tumor DNA yielded two discrete products, one identical to normal, and a second smaller one. Direct sequencing revealed that the nontumor tissue contained 24 CAGs, whereas the tumor contained one fragment with 24 CAGs (wild-type) and a second fragment with 18 CAGs (mutant), representing a somatic contraction of the AR CAG repeat (CAG24→CAG18) in the tumor. Interestingly, this patient manifested a paradoxical agonistic response to hormonal therapy with the antiandrogen flutamide.