Detection of tumor ALK status in neuroblastoma patients using peripheral blood.
Detection of tumor ALK status in neuroblastoma patients using peripheral blood.
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DOI：
10.1002/cam4.414
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发表时间：
2015-04
期刊：
影响因子：
4
通讯作者：
Blay, Jean Yves
中科院分区：
文献类型：
--
作者：
Combaret, Valerie;Iacono, Isabelle;Bellini, Angela;Brejon, Stephanie;Bernard, Virginie;Marabelle, Aurelien;Coze, Carole;Pierron, Gaelle;Lapouble, Eve;Schleiermacher, Gudrun;Blay, Jean Yves
基于克唑替尼或其他ALK靶向分子的ALK靶向治疗的新方案已经开放，用于治疗神经母细胞瘤（NB）患者，如果他们的肿瘤显示ALK基因突变和/或扩增。然而，肿瘤样本并不总是可用来分析ALK突变状态，特别是在复发时。在这里，我们利用液滴数字PCR （ddPCR）系统，通过分析循环DNA来评估NB样品的ALK突变状态。建立了用于NB肿瘤中F1174和R1275热点ALK突变检测的ddPCR方法，并应用于114例NB患者200 μL血清或血浆样本的循环DNA分析。在循环DNA中检测到突变F1174L（23外显子位置3520，T b> C和3522，C>A）和突变R1275Q（25外显子位置3824，G>A）。本试验的灵敏度分别为100%、85%和92%，特异性分别为100%、91%和98%。总之，我们开发的检测提供了一种可靠的、无创的血液检测来评估F1174和R1275热点的ALK突变状态，并应帮助临床医生识别显示ALK突变的患者，特别是在没有肿瘤组织的情况下。
New protocols based on ALK-targeted therapy by crizotinib or other ALK-targeting molecules have opened for the treatment of patients with neuroblastoma (NB) if their tumors showed mutation and/or amplification of the ALK gene. However, tumor samples are not always available for analysis of ALK mutational status in particular at relapse. Here, we evaluated the ALK mutational status of NB samples by analysis of circulating DNA, using the droplet digital PCR (ddPCR) system. ddPCR assays was developed for the detection of ALK mutations at F1174 and R1275 hotspots found in NB tumors and was applied for the analysis of circulating DNA obtained from 200 μL of serum or plasma samples collected from 114 patients with NB. The mutations F1174L (exon 23 position 3520, T>C and position 3522, C>A) and the mutation R1275Q (exon 25 position 3824, G>A) were detected in circulating DNA. The sensitivity of our test was 100%, 85%, and 92%, respectively, and the specificity was 100%, 91%, and 98%, respectively. In conclusion, the assay that we have developed offers a reliable, noninvasive blood test to assess ALK mutational status at F1174 and R1275 hotspots and should help clinicians to identify patients showing an ALK mutation in particular when no tumor tissue is available.
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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
影响因子：
45.3
作者：
BRODEUR, GM;PRITCHARD, J;VOUTE, PA
通讯作者：
VOUTE, PA
影响因子：
9.3
作者：
Chan, K. C. Allen;Jiang, Peiyong;Lo, Y. M. D.
通讯作者：
Lo, Y. M. D.
影响因子：
3.7
作者：
Page K;Guttery DS;Zahra N;Primrose L;Elshaw SR;Pringle JH;Blighe K;Marchese SD;Hills A;Woodley L;Stebbing J;Coombes RC;Shaw JA
通讯作者：
Shaw JA
影响因子：
7.4
作者：
Hindson, Benjamin J.;Ness, Kevin D.;Masquelier, Donald A.;Belgrader, Phillip;Heredia, Nicholas J.;Makarewicz, Anthony J.;Bright, Isaac J.;Lucero, Michael Y.;Hiddessen, Amy L.;Legler, Tina C.;Kitano, Tyler K.;Hodel, Michael R.;Petersen, Jonathan F.;Wyatt, Paul W.;Steenblock, Erin R.;Shah, Pallavi H.;Bousse, Luc J.;Troup, Camille B.;Mellen, Jeffrey C.;Wittmann, Dean K.;Erndt, Nicholas G.;Cauley, Thomas H.;Koehler, Ryan T.;So, Austin P.;Dube, Simant;Rose, Klint A.;Montesclaros, Luz;Wang, Shenglong;Stumbo, David P.;Hodges, Shawn P.;Romine, Steven;Milanovich, Fred P.;White, Helen E.;Regan, John F.;Karlin-Neumann, George A.;Hindson, Christopher M.;Saxonov, Serge;Colston, Bill W.
通讯作者：
Colston, Bill W.