Comparison of Molecular Testing Modalities for Detection of ROS1 Rearrangements in a Cohort of Positive Patient Samples.
Comparison of Molecular Testing Modalities for Detection of ROS1 Rearrangements in a Cohort of Positive Patient Samples.
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DOI：
10.1016/j.jtho.2018.05.041
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Doebele RC
中科院分区：
文献类型：
--
作者：
Davies KD;Le AT;Sheren J;Nijmeh H;Gowan K;Jones KL;Varella-Garcia M;Aisner DL;Doebele RC
在约1-2%的非小细胞肺癌患者中发现ROS1基因融合是一类特征明确的致癌驱动因子。与化疗相比，这些患者的ros1定向治疗更有效，副作用更少，因此现在被认为是晚期疾病患者的标准治疗方法。因此，准确检测临床肿瘤样本中的ROS1重排/融合是至关重要的。在这项研究中，我们比较了三种常见的分子检测方法在ROS1重排/融合阳性患者样本中的表现。23例ROS1重排/融合阳性临床样本通过以下至少两种分子检测方法进行评估：分离荧光原位杂交（FISH），基于dna的杂交捕获文库制备，然后进行下一代测序（NGS），以及基于rna的锚定多重PCR文库制备，然后进行NGS。没有一种检测方法在检测ROS1重排/融合方面表现出100%的灵敏度。20个测试样本中有2个FISH结果为阴性，18个测试样本中有4个基于dna的NGS检测结果为阴性，19个测试样本中有3个基于rna的NGS检测结果为阴性。对于所有三种检测方法，我们确定了可能导致假阴性结果的分析特征。此外，我们报告说，基因组断点是一个不可靠的预测断点在转录水平，可能是由于选择性剪接。临床环境中的ROS1重排/融合检测是复杂的，所有方法都有固有的局限性，用户必须意识到这些局限性，以便正确解释结果。
ROS1 gene fusions are a well-characterized class of oncogenic driver found in approximately 1-2% of non-small cell lung cancer patients. ROS1-directed therapy in these patients is more efficacious and is associated with fewer side effects compared to chemotherapy and is thus now considered standard-of-care for patients with advanced disease. Consequently, accurate detection of ROS1 rearrangements/fusions in clinical tumor samples is vital. In this study, we compared the performance of three common molecular testing approaches on a cohort of ROS1 rearrangement/fusion-positive patient samples. Twenty-three ROS1 rearrangement/fusion-positive clinical samples were assessed by at least two of the following molecular testing methodologies: break-apart fluorescence in situ hybridization (FISH), DNA-based hybrid capture library preparation followed by next-generation sequencing (NGS), and RNA-based anchored multiplex PCR library preparation followed by NGS. None of the testing methodologies demonstrated 100% sensitivity in detection of ROS1 rearrangements/fusions. FISH results were negative in 2 out of 20 tested samples, the DNA-based NGS assay was negative in 4 out of 18 tested samples, and the RNA-based NGS assay was negative in 3 of 19 tested samples. For all three testing approaches, we identified assay characteristics that likely contributed to false-negative results. Additionally, we report that genomic breakpoints are an unreliable predictor of breakpoints at the transcript level, likely due to alternative splicing. ROS1 rearrangement/fusion detection in the clinical setting is complex and all methodologies have inherent limitations of which users must be aware in order to correctly interpret results.
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影响因子：
4.6
作者：
Davies KD;Ng TL;Estrada-Bernal A;Le AT;Ennever PR;Camidge DR;Doebele RC;Aisner DL
通讯作者：
Aisner DL
DOI：
10.1158/1078-0432.ccr-12-0838
发表时间：
2012-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Suehara Y;Arcila M;Wang L;Hasanovic A;Ang D;Ito T;Kimura Y;Drilon A;Guha U;Rusch V;Kris MG;Zakowski MF;Rizvi N;Khanin R;Ladanyi M
通讯作者：
Ladanyi M
DOI：
10.1158/1078-0432.ccr-12-0550
发表时间：
2012-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Davies KD;Le AT;Theodoro MF;Skokan MC;Aisner DL;Berge EM;Terracciano LM;Cappuzzo F;Incarbone M;Roncalli M;Alloisio M;Santoro A;Camidge DR;Varella-Garcia M;Doebele RC
通讯作者：
Doebele RC
影响因子：
51.1
作者：
Drilon, Alexander;Rekhtman, Natasha;Arcila, Maria;Wang, Lu;Ni, Andy;Albano, Melanie;Van Voorthuysen, Martine;Somwar, Romel;Smith, Roger S.;Montecalvo, Joseph;Plodkowski, Andrew;Ginsberg, Michelle S.;Riely, Gregory J.;Rudin, Charles M.;Ladanyi, Marc;Kris, Mark G.
通讯作者：
Kris, Mark G.
影响因子：
3.8
作者：
Wu, Jieyu;Lin, Yunen;Gu, Xia
通讯作者：
Gu, Xia