Novel TRAF1-ALK Fusion Identified by Deep RNA Sequencing of Anaplastic Large Cell Lymphoma
Novel TRAF1-ALK Fusion Identified by Deep RNA Sequencing of Anaplastic Large Cell Lymphoma
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DOI：
10.1002/gcc.22104
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发表时间：
2013-11-01
影响因子：
3.7
通讯作者：
Caride, Ariel
中科院分区：
文献类型：
--
作者：
Feldman, Andrew L.;Vasmatzis, George;Caride, Ariel
导致异常融合蛋白表达的染色体易位在各种血液恶性肿瘤的发病机制中发挥着重要作用。最近高通量深度测序的发展使得新的易位的发现成为可能，从而使人们对这些疾病的了解迅速增加。涉及间变性淋巴瘤激酶 (ALK) 基因导致 ALK 融合蛋白的易位最初是在间变性大细胞淋巴瘤 (ALCL) 中发现的。在 ALCL 中，NPM1-ALK 融合最常见，并导致融合蛋白的核定位。在这里，我们展示了一名患有 ALCL 的 50 岁男性，仅表现出细胞质 ALK 免疫反应性，表明存在非 NPM1 融合伴侣。我们对该患者的肿瘤组织进行了深度 RNA 测序，并鉴定了一个将 TRAF1 的外显子 6 与 ALK 的外显子 20 融合的新转录本。通过 Sanger 测序在 mRNA 水平上确认 TRAF1-ALK 融合转录物，并通过蛋白质印迹使融合蛋白可视化。这种 TRAF1-ALK 融合的发现扩大了已知 ALK 融合伙伴的多样性，并凸显了深度测序在发现融合转录本方面的力量。 (c) 2013 年 Wiley 期刊公司。
Chromosomal translocations leading to expression of abnormal fusion proteins play a major role in the pathogenesis of various hematologic malignancies. The recent development of high-throughput, deep sequencing has allowed discovery of novel translocations leading to a rapid increase in understanding these diseases. Translocations involving the anaplastic lymphoma kinase (ALK) gene leading to ALK fusion proteins originally were discovered in anaplastic large cell lymphomas (ALCLs). Among ALCLs, NPM1-ALK fusions are most common and lead to nuclear localization of the fusion protein. Here, we present a 50-year-old male with ALCL demonstrating cytoplasmic ALK immunoreactivity only, suggesting the presence of a non-NPM1 fusion partner. We performed deep RNA sequencing of tumor tissue from this patient and identified a novel transcript fusing Exon 6 of TRAF1 to Exon 20 of ALK. The TRAF1-ALK fusion transcript was confirmed at the mRNA level by Sanger sequencing and the fusion protein was visualized by Western blot. The discovery of this TRAF1-ALK fusion expands the diversity of known ALK fusion partners and highlights the power of deep sequencing for fusion transcript discovery. (c) 2013 Wiley Periodicals, Inc.