Identification of EML4-ALK as an alternative fusion gene in epithelioid inflammatory myofibroblastic sarcoma.
Identification of EML4-ALK as an alternative fusion gene in epithelioid inflammatory myofibroblastic sarcoma.
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DOI：
10.1186/s13023-017-0647-8
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发表时间：
2017-05-23
影响因子：
3.7
通讯作者：
Lu WQ
中科院分区：
文献类型：
--
作者：
Jiang Q;Tong HX;Hou YY;Zhang Y;Li JL;Zhou YH;Xu J;Wang JY;Lu WQ
被称为中等恶性潜能的实体瘤，只要肿瘤被整块切除，大多数炎性肌纤维母细胞瘤（IMT）是可治疗的。然而，在某些情况下，肿瘤在成功手术后复发并迅速生长。其中一些肿瘤被归类为上皮样炎性肌纤维母细胞肉瘤（EIMS）。大多数先前报道的EIMS由RANBP 2-ALK融合基因引起。我们在此报告一例EML 4-ALK融合基因引起的EIMS病例。采用RNAseq技术寻找新的ALK融合基因，该融合基因在先前报道的RANBP 2-ALK融合基因的EIMS病例中采用RT-PCR方法无法检测到。之后，我们还进行了RT-PCR，以进一步证明新发现的融合基因。应用免疫组化（IHC）和荧光原位杂交（FISH）技术，与以往报道的EIMS病例进行比较，发现其独特的形态学特征。我们发现一位EIMS患者，在接受细胞减灭术以减轻恶化的症状后，迅速复发。该患者最终在应用克唑替尼后死于肿瘤溶解综合征。还可以观察到膜下的独特ALK染色和细胞质中相对较弱的ALK染色。RNAseq和RT-PCR进一步显示肿瘤携带EML 4-ALK融合基因。总之，这是第一个证明由EML 4-ALK融合基因形成引起的EIMS。这丰富了EIMS的研究内容，拓宽了EIMS的研究视野。我们通过讨论其成功和失败的方面来分享管理这种疾病的经验，这对外科医生和病理学家来说可能具有很大的价值。本文的在线版本（doi：10.1186/s13023-017-0647-8）包含补充材料，可供授权用户使用。
Known as solid tumors of intermediate malignant potential, most inflammatory myofibroblastic tumors (IMTs) are treatable as long as the tumor is en-bloc resected. However, in some cases, the tumors have recurred and grown rapidly after successful surgery. Some of these tumors were classified as an epithelioid inflammatory myofibroblastic sarcoma (EIMS). Most previously reported EIMSs have been caused by RANBP2-ALK fusion gene. We herein report an EIMS case caused by an EML4-ALK fusion gene. RNAseq was conducted to find out the new ALK fusion gene which could not be detected following previously reported RT-PCR methods for EIMS cases with RANBP2-ALK fusion gene. After that, RT-PCR was also conducted to further prove the newly found fusion gene. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) test were applied to find out the unique morphological characters compared with the previous reported EIMS cases. We found an EIMS case who was suffering from a rapid recurrence after cytoreducyive surgery was done to relieve the exacerbating symptoms. The patient finally died for tumor lysis syndrome after the application of crizotinib. Distinctive ALK staining under the membrane and relatively weak ALK staining in the cytoplasm could also be observed. RNAseq and RT-PCR further revealed that the tumor harbored an EML4-ALK fusion gene. In conclusion, this is the first EIMS demonstrated to have been caused by the formation of an EML4-ALK fusion gene. This enriches the spectrum of EIMS and enlarges the horizon for the study of EIMS. The experience we shared in managing this kind of disease by discussing aspects of its success and failure could be of great value for surgeons and pathologists. The online version of this article (doi:10.1186/s13023-017-0647-8) contains supplementary material, which is available to authorized users.