Allelic imbalance on 12q22-23 in serum circulating DNA of melanoma patients predicts disease outcome

Allelic imbalance on 12q22-23 in serum circulating DNA of melanoma patients predicts disease outcome
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DOI:
10.1158/0008-5472.can-04-0957
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发表时间:
2004-06-15
期刊:
影响因子:
11.2
通讯作者:
Hoon, DSB
Hoon, DSB
中科院分区:
医学1区
文献类型:
--
作者:
Fujimoto, A;O'Day, SJ;Hoon, DSB

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在转移性黑色素瘤中经常发现包含凋亡蛋白酶激活因子1(APAF-1)基因座(12q22 - 23)的等位基因失衡(AI)。将血清中12q22 - 23上具有AI的循环DNA作为预测黑色素瘤患者生物化疗(BC)治疗反应的替代标志物进行评价。从49名用BC治疗的美国癌症联合委员会IV期黑素瘤患者收集血清。血清12q22 - 23区AI在BC前和/或BC后均存在。BC应答者的AI频率(5/24,21%)显著低于无应答者(11/20,55%; Fisher精确检验,P <0.029)。12q22 - 23的血清AI与预后相关(logrank检验,P <0.046)。这些发现表明,12q22 - 23上肿瘤相关AI的系列血清遗传分析可能在预测肿瘤对治疗的反应方面具有临床用途。
Allelic imbalance (AI) encompassing the apoptotic protease-activating factor 1 (APAF-1) locus (12q22-23) is found frequently in metastatic melanoma. Circulating DNA with AI on 12q22-23 in serum was evaluated as a surrogate marker to predict biochemotherapy (BC) treatment response in melanoma patients. Sera were collected from 49 American Joint Committee on Cancer stage IV melanoma patients treated with BC. Serum AI of the 12q22-23 region was demonstrated to be present before and/or after BC. BC responders showed a significantly lower frequency of AI (5 of 24, 21%) compared with nonresponders (11 of 20, 55%; Fisher's exact test, P < 0.029). Serum AI on 12q22-23 was associated with worse prognosis (log-rank test, P < 0.046). These findings indicate that serial serum genetic analysis of tumor-related AI on 12q22-23 may have clinical use in predicting tumor response to therapy.