Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma.
Implementation of the plasma MYCN/NAGK ratio to detect MYCN amplification in patients with neuroblastoma.
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DOI：
10.1002/1878-0261.12794
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发表时间：
2020-11
影响因子：
6.6
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
Su Y;Wang L;Zhao Q;Yue Z;Zhao W;Wang X;Duan C;Jin M;Zhang D;Chen S;Yin J;Qiu L;Cheng X;Xu Z;Ma X
检测MYCN基因扩增对于评估神经母细胞瘤患者的治疗和预后至关重要。我们开发了一种利用血浆DNA定量PCR检测MYCN扩增的方法。血浆中MYCN拷贝数的增加与MYCN扩增一致，DNA - FISH评估了神经母细胞瘤患者的MYCN扩增。检测MYCN基因扩增对于确定神经母细胞瘤（NB）患者的最佳治疗和估计预后至关重要。神经母细胞瘤组织或患者来源的骨髓细胞DNA FISH是检测MYCN扩增的标准临床实践。由于肿瘤细胞可能经常无法获得，我们开发了一种检测成神经细胞瘤患者血浆中MYCN扩增的方法。以单拷贝NAGK DNA为参照，我们采用实时定量PCR （real - time quantitative PCR, qPCR）测定了115例NB患者血浆中MYCN/NAGK的比值。血浆中MYCN/NAGK比值升高与DNA FISH评估的MYCN扩增一致。MYCN/NAGK比值为6.965时，AUC为0.943，敏感性为86%，特异性为100%。超过6.965的阈值，MYCN/NAGK比值与较重的肿瘤负担相关。MYCN/NAGK比值高于6.965的4期患者的无事件生存期和2年总生存期显著缩短。在病情进展和复发的患者中，血浆MYCN/NAGK比值升高。因此，我们得出结论，用qPCR测定血浆MYCN/NAGK比值是一种无创且可重复的方法来测量NB患者的MYCN扩增。
Detection of amplification of the MYCN gene is essential for estimating treatment and prognosis of patients with neuroblastoma. We developed a method to detect MYCN amplification using the plasma DNA by quantitative PCR. An increase in MYCN copies in the plasma was consistent with MYCN amplification as assessed by DNA‐FISH to measure MYCN amplification in patients with neuroblastoma. Detection of amplification of the MYCN gene is essential for determining optimal treatment and estimating prognosis of patients with neuroblastoma (NB). DNA FISH with neuroblastoma tissues or patient‐derived bone marrow cells is the standard clinical practice for the detection of MYCN amplification. As tumor cells may often be unavailable, we developed a method to detect MYCN amplification in the plasma of patients with neuroblastoma. Taking single‐copy NAGK DNA as reference, we used real‐time quantitative PCR (qPCR) to determine the MYCN/NAGK ratio in the plasma of 115 patients diagnosed with NB. An increased MYCN/NAGK ratio in the plasma was consistent with MYCN amplification as assessed by DNA FISH. The AUC for a MYCN/NAGK ratio equal to 6.965 was 0.943, with 86% sensitivity and 100% specificity. Beyond the threshold of 6.965, the MYCN/NAGK ratio correlated with a heavier tumor burden. Event‐free and overall survival of two years were significantly shortened in stage 4 patients with a MYCN/NAGK ratio higher than 6.965. Plasma MYCN/NAGK ratios increased in patients with progressive disease and relapse. Thus, we conclude that the determination of the plasma MYCN/NAGK ratio by qPCR is a noninvasive and reproducible method to measure MYCN amplification in patients with NB.
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影响因子：
3.2
作者：
Combaret, Valerie;Hogarty, Michael D.;Puisieux, Alain
通讯作者：
Puisieux, Alain
DOI：
10.1007/s40272-017-0251-3
发表时间：
2017-12
期刊：
Paediatric drugs
影响因子：
--
作者：
Berthold F;Spix C;Kaatsch P;Lampert F
通讯作者：
Lampert F
影响因子：
45.3
作者：
Cheung, Nai-Kong V.;Ostrovnaya, Irina;Cheung, Irene Y.
通讯作者：
Cheung, Irene Y.
影响因子：
3.2
作者：
Campbell, Kevin;Shyr, Derek;DuBois, Steven G.
通讯作者：
DuBois, Steven G.
影响因子：
1.2
作者：
Kobayashi, Kenichiro;Mizuta, Shumpei;Heike, Toshio
通讯作者：
Heike, Toshio