Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions.
Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions.
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DOI：
10.1158/2159-8290.cd-14-0377
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发表时间：
2014-08
期刊：
影响因子：
28.2
通讯作者：
Coffin CM
中科院分区：
文献类型：
--
作者：
Lovly CM;Gupta A;Lipson D;Otto G;Brennan T;Chung CT;Borinstein SC;Ross JS;Stephens PJ;Miller VA;Coffin CM
炎性肌纤维母细胞瘤（IMT）是一种常见于儿童的肿瘤。这种肿瘤的遗传景观尚未完全了解，治疗选择有限。虽然50%的IMT具有ALK重排，但在ALK阴性肿瘤中尚未确定治疗靶点。我们首次报道了IMT具有其他可操作的靶点，包括ROS 1和PDGFRβ融合。我们详细的情况下，8岁的男孩与治疗难治性ALK阴性IMT。分子肿瘤分析显示了ROS1融合，他对ROS1抑制剂克唑替尼有显著的反应。该病例促使对更大系列的IMT进行评估。下一代测序显示，85%的评估病例携带激酶融合，涉及ALK、ROS 1或PDGFRβ。我们的研究代表了迄今为止对IMT最全面的遗传分析，也为这些肿瘤的常规分子分析提供了基本原理，以检测可治疗的激酶融合。
Inflammatory myofibroblastic tumor (IMT) is a neoplasm which typically occurs in children. The genetic landscape of this tumor is incompletely understood and therapeutic options are limited. While 50% of IMTs harbor ALK rearrangements, no therapeutic targets have been identified in ALK negative tumors. We report for the first time that IMTs harbor other actionable targets, including ROS1 and PDGFRβ fusions. We detail the case of an 8 year old boy with treatment-refractory ALK negative IMT. Molecular tumor profiling revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor, crizotinib. This case prompted assessment of a larger series of IMTs. Next generation sequencing revealed that 85% of cases evaluated harbored kinase fusions, involving ALK, ROS1, or PDGFRβ. Our study represents the most comprehensive genetic analysis of IMTs to date and also provides rationale for routine molecular profiling of these tumors to detect therapeutically actionable kinase fusions.