Systematic Screen for Tyrosine Kinase Rearrangements Identifies a Novel C6orf204-PDGFRB Fusion in a Patient with Recurrent T-ALL and an Associated Myeloproliferative Neoplasm
Systematic Screen for Tyrosine Kinase Rearrangements Identifies a Novel C6orf204-PDGFRB Fusion in a Patient with Recurrent T-ALL and an Associated Myeloproliferative Neoplasm
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DOI：
10.1002/gcc.20930
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发表时间：
2012-01-01
影响因子：
3.7
通讯作者：
Pao, William
中科院分区：
文献类型：
--
作者：
Chmielecki, Juliann;Peifer, Martin;Pao, William
涉及酪氨酸激酶(TKS)催化结构域的基因融合在多种血液系统和实体肿瘤中被发现。临床上，TK融合已成为小分子激酶抑制剂治疗的主要靶点。不幸的是，TK融合的鉴定受到实验限制的阻碍。在这里，我们开发了一种基于基因组的系统激酶融合筛查的2.0版本，并使用它来检测一名患有前体T淋巴母细胞淋巴瘤(T-ALL)和与嗜酸性粒细胞增多相关的骨髓增生性肿瘤的患者中新的伊马替尼敏感的C6orf204-PDGFRb融合。这些数据验证了这种定向捕获-测序方法在直接从患者样本中提取的少量DNA中检测TK融合事件的能力。(C)2011年威利期刊公司。
Gene fusions involving the catalytic domain of tyrosine kinases (TKs) are found in a variety of hematological and solid tumor malignancies. Clinically, TK fusions have emerged as prime targets for therapy with small molecule kinase inhibitors. Unfortunately, identification of TK fusions has been hampered by experimental limitations. Here, we developed version 2.0 of a genomically based systematic kinase fusion screen and used it to detect a novel imatinib-sensitive C6orf204-PDGFRB fusion in a patient with precursor T lymphoblastic lymphoma (T-ALL) and an associated myeloproliferative neoplasm with eosinophilia. These data validate the ability of this targeted capture-sequencing approach to detect TK fusion events in small amounts of DNA extracted directly from patient samples. (C) 2011 Wiley Periodicals, Inc.