使用NanoString nCounter系统对小儿低级别胶质瘤特征性融合转录本和重复进行多重检测。
Multiplex Detection of Pediatric Low-Grade Glioma Signature Fusion Transcripts and Duplications Using the NanoString nCounter System.
作者信息
Ryall Scott, Arnoldo Anthony, Krishnatry Rahul, Mistry Matthew, Khor Kangzi, Sheth Javal, Ling Cino, Leung Stephie, Zapotocky Michal, Guerreiro Stucklin Ana, Lassaletta Alvaro, Shago Mary, Tabori Uri, Hawkins Cynthia E
机构信息
Department of Cancer and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Divisions of Pathology and Genome Diagnostics, Department of Paediatric Laboratory Medicine; and Division of Hematology and Oncology, The Division of Hematology and Oncology should be followed by Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada. Hospital for Sick Children, Toronto, Ontario, Canada; Department of Radiation Oncology, Tata Memorial Hospital, Parel, Mumbai, India; and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
出版信息
J Neuropathol Exp Neurol. 2017 Jul 1;76(7):562-570. doi: 10.1093/jnen/nlx042.
Previous studies identified recurrent fusion and duplication events in pediatric low-grade glioma (pLGG). In addition to their role in diagnosis, the presence of these events aid in dictating therapy and predicting patient survival. Clinically, BRAF alterations are most commonly identified using fluorescent in situ hybridization (FISH). However, this method is costly, labor-intensive and does not identify nonBRAF events. Here, we evaluated the NanoString nCounter gene expression system for detecting 32 of the most commonly reported fusion/duplication events in pLGG. The assay was validated on 90 pLGG samples using FISH as the gold standard and showed sensitivity and specificity of 97% and 98%, respectively. We next profiled formalin-fixed paraffin-embedded preserved biopsy specimens from 429 pLGG cases. 171 (40%) of the cases within our cohort tested positive for a fusion or duplication event contained within our panel. These events, in order of prevalence, were KIAA1549-BRAF 16;9 (89/171, 52.0%), KIAA1549-BRAF 15;9 (42/171, 24.6%), KIAA1549-BRAF 16;11 (14/171, 8.2%), FGFR1-TACC1 17;7 (13/171, 7.6%), MYBL1 duplication (5/171, 2.9%), KIAA1549-BRAF 18;10 (4/171, 2.3%), KIAA1549-BRAF 15;11 (2/171, 1.2%), FAM131B-BRAF 2;9 (1/171, 0.6%), and RNF130-BRAF 3;9 (1/171, 0.6%). This work introduces NanoString as a viable clinical replacement for the detection of fusion and duplication events in pLGG.
先前的研究在儿童低级别胶质瘤（pLGG）中发现了反复出现的融合和重复事件。除了在诊断中的作用外，这些事件的存在有助于指导治疗并预测患者的生存期。临床上，BRAF改变最常用荧光原位杂交（FISH）来识别。然而，这种方法成本高、劳动强度大，且无法识别非BRAF事件。在此，我们评估了NanoString nCounter基因表达系统用于检测pLGG中32种最常报道的融合/重复事件。该检测方法以FISH作为金标准在90份pLGG样本上进行了验证，灵敏度和特异性分别为97%和98%。接下来，我们对429例pLGG病例的福尔马林固定石蜡包埋保存活检标本进行了分析。在我们的队列中，171例（40%）病例检测出我们检测板中包含的融合或重复事件呈阳性。这些事件按发生率排序依次为：KIAA1549-BRAF 16; nine (89/171, 52.0%)、KIAA1549-BRAF 15; nine (42/171, 24.6%)、KIAA1549-BRAF 16; eleven (14/171, 8.2%)、FGFR1-TACC1 17; seven (13/171, 7.6%)、MYBL1重复 (5/171, 2.9%)、KIAA1549-BRAF 18; ten (4/171, 2.3%)、KIAA1549-BRAF 15; eleven (2/171, 1.2%)、FAM131B-BRAF 2; nine (1/171, 0.6%) 和RNF130-BRAF 3; nine (1/171, 0.6%)。这项工作引入了NanoString作为检测pLGG中融合和重复事件的一种可行的临床替代方法。
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