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首頁> 外文期刊>Clinical Chemistry: Journal of the American Association for Clinical Chemists >Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer.
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Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer.

機(jī)譯:去勢(shì)抵抗性前列腺癌中循環(huán)腫瘤細(xì)胞中雄激素受體突變的檢測(cè)。

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BACKGROUND: Coding mutations in the AR (androgen receptor) gene have been identified in tissue samples from patients with advanced prostate cancer and represent a possible mechanism underlying the development of castration-resistant prostate cancer (CRPC). There is a paucity of tumor-derived tissue available for molecular studies of CRPC patients. Circulating tumor cells (CTCs) in the blood of CRPC patients represent a possible avenue for interrogating the disease of such patients. METHODS: Circulating tumor cells were captured with the CellSearch Circulating Tumor Cell (CTC) Kit and with the CellSearch Profile Kit plus Qiagen's AllPrep DNA/RNA Micro Kit for the measurement of the CTC count per 7.5 mL of blood and for the isolation of nucleic acids, respectively. The AR gene was amplified by the PCR, and mutation status and relative abundance were analyzed by applying Transgenomic's WAVE denaturing HPLC technology followed by direct sequencing. RESULTS: AR mutations were detected in 20 of 35 CRPC patients; 19 missense mutations, 2 silent mutations, 5 deletions, and 1 insertion were observed. The relative abundance of the mutants in the amplified products ranged from 5% to 50%. Many of the AR mutations were identified in surgical biopsies or at autopsy and were associated with resistance to androgen-directed therapies. CONCLUSIONS: AR mutations can be identified in CTC-enriched peripheral blood samples from CRPC patients. This approach has the potential to open new perspectives in understanding CTCs and the mechanisms for tumor progression and metastasis in CRPC.
機(jī)譯:背景:AR(雄激素受體)基因的編碼突變已在晚期前列腺癌患者的組織樣本中鑒定出來,并代表了去勢(shì)抵抗性前列腺癌(CRPC)發(fā)展的潛在機(jī)制。很少有腫瘤來源的組織可用于CRPC患者的分子研究。 CRPC患者血液中的循環(huán)腫瘤細(xì)胞(CTC)代表了詢問此類患者疾病的可能途徑。方法:使用CellSearch循環(huán)腫瘤細(xì)胞(CTC)試劑盒和CellSearch Profile Kit加上Qiagen的AllPrep DNA / RNA Micro試劑盒捕獲循環(huán)腫瘤細(xì)胞,以測(cè)量每7.5 mL血液中的CTC數(shù)量并分離核酸, 分別。通過PCR擴(kuò)增AR基因,并應(yīng)用Transgenomic的WAVE變性HPLC技術(shù)分析突變狀態(tài)和相對(duì)豐度,然后進(jìn)行直接測(cè)序。結(jié)果:35例CRPC患者中有20例檢測(cè)到AR突變。觀察到19個(gè)錯(cuò)義突變,2個(gè)沉默突變,5個(gè)缺失和1個(gè)插入。擴(kuò)增產(chǎn)物中突變體的相對(duì)豐度為5%至50%。許多AR突變是在手術(shù)活檢或尸檢中發(fā)現(xiàn)的,并且與對(duì)雄激素定向療法的耐藥性有關(guān)。結(jié)論:可以在來自CRPC患者的富含CTC的外周血樣本中鑒定出AR突變。這種方法有可能為了解CTC以及CRPC中腫瘤進(jìn)展和轉(zhuǎn)移的機(jī)制開辟新的前景。

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