通过荧光原位杂交检测16例软组织透明细胞肉瘤和6例胃肠道透明细胞肉瘤样肿瘤中的特定基因重排。
Detection of specific gene rearrangements by fluorescence in situ hybridization in 16 cases of clear cell sarcoma of soft tissue and 6 cases of clear cell sarcoma-like gastrointestinal tumor.
作者信息
Segawa Keiko, Sugita Shintaro, Aoyama Tomoyuki, Kubo Terufumi, Asanuma Hiroko, Sugawara Taro, Ito Yumika, Tsujiwaki Mitsuhiro, Fujita Hiromi, Emori Makoto, Hasegawa Tadashi
机构信息
Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, 060-8543, Japan.
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, 060-8556, Japan.
出版信息
Diagn Pathol. 2018 Sep 15;13(1):73. doi: 10.1186/s13000-018-0752-6.
BACKGROUND
Clear cell sarcoma of soft tissue (CCSST) and clear cell sarcoma-like gastrointestinal tumor (CCSLGT) are malignant mesenchymal tumors that share some pathological features, but they also have several different characteristics. They are well known to express chimeric fusions of Ewing sarcoma breakpoint region 1 (EWSR1) and cAMP response element-binding protein (CREB) family members; namely, EWSR1-activating transcription factor 1 (ATF1) and EWSR1-CREB1. In addition, recent studies have suggested the presence of other fusions.
METHODS
We used fluorescence in situ hybridization to detect specific rearrangements including EWSR1, ATF1, CREB1, and cAMP response element modulator (CREM) in 16 CCSST and 6 CCSLGT cases. We also used reverse transcription polymerase chain reaction (RT-PCR) to detect specific chimeric fusions of EWSR1-ATF1 and EWSR1-CREB1 using fresh tumor samples in available cases.
RESULTS
A total of 15 of 16 CCSST cases (93.8%) had EWSR1 rearrangement, of which 11 (68.8%) also had ATF1 rearrangement, suggestive of the presence of EWSR1-ATF1 fusions. One CCSST case (6.3%) was found to have EWSR1 and CREM rearrangements, and 4 of 6 CCSLGT cases (66.7%) had EWSR1 rearrangement, of which 2 (33.3%) showed ATF1 rearrangement and the other 2 cases (33.3%) showed CREB1 rearrangement. These cases most likely had EWSR1-ATF1 and EWSR1-CREB1 fusions, respectively. RT-PCR was performed in 8 available cases, including 6 CCSSTs and 2 CCSLGTs. All CCSSTs showed EWSR1-ATF1 fusions. Among the 2 CCSLGT cases, one had EWSR1-ATF1 fusion and the other had EWSR1-CREB1 fusion.
CONCLUSIONS
Rearrangements of EWSR1 and ATF1 or EWSR1-ATF1 fusion were predominantly found in CCSST, whereas those of EWSR1 and CREB1 or EWSR1-CREB1 tended to be detected in CCSLGT. A novel CREM fusion was also detected in a few cases of CCSST and CCSLGT. The cases in which EWSR1 rearrangement was detected without definitive partner genes should be considered for the presence of CREM rearrangement.
背景
软组织透明细胞肉瘤（CCSST）和透明细胞肉瘤样胃肠道肿瘤（CCSLGT）是具有一些共同病理特征的恶性间叶性肿瘤，但它们也有一些不同的特点。众所周知，它们会表达尤文肉瘤断点区域1（EWSR1）与环磷酸腺苷反应元件结合蛋白（CREB）家族成员的嵌合融合体，即EWSR1-激活转录因子1（ATF1）和EWSR1-CREB1。此外，最近的研究提示还存在其他融合体。
方法
我们采用荧光原位杂交技术检测了16例CCSST和6例CCSLGT病例中包括EWSR1、ATF1、CREB1和环磷酸腺苷反应元件调节剂（CREM）在内的特定重排。我们还利用逆转录聚合酶链反应（RT-PCR），对可用病例中的新鲜肿瘤样本检测了EWSR1-ATF1和EWSR1-CREB1的特定嵌合融合体。
结果
16例CCSST病例中有15例（93.8%）发生EWSR1重排，其中11例（68.8%）也有ATF1重排，提示存在EWSR1-ATF1融合体。1例CCSST病例（6.3%）被发现有EWSR1和CREM重排，6例CCSLGT病例中有4例（66.7%）发生EWSR1重排，其中2例（33.3%）显示ATF1重排，另外2例（33.3%）显示CREB1重排。这些病例很可能分别存在EWSR1-ATF1和EWSR1-CREB1融合体。对8例可用病例进行了RT-PCR检测，包括6例CCSST和2例CCSLGT。所有CCSST均显示EWSR1-ATF1融合体。在2例CCSLGT病例中，1例有EWSR1-ATF1融合体，另1例有EWSR1-CREB1融合体。
结论
EWSR1和ATF1重排或EWSR1-ATF1融合体主要见于CCSST，而EWSR1和CREB1重排或EWSR1-CREB1重排则倾向于在CCSLGT中检测到。在少数CCSST和CCSLGT病例中还检测到一种新的CREM融合体。对于检测到EWSR1重排但无明确伙伴基因的病例，应考虑存在CREM重排。
Zotero 插件