Identification of COL3A1 and RAB2A as Novel Translocation Partner Genes of PLAG1 in Lipoblastoma
Identification of COL3A1 and RAB2A as Novel Translocation Partner Genes of PLAG1 in Lipoblastoma
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DOI：
10.1002/gcc.22170
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发表时间：
2014-07-01
影响因子：
3.7
通讯作者：
Hosoi, Hajime
中科院分区：
文献类型：
--
作者：
Yoshida, Hideki;Miyachi, Mitsuru;Hosoi, Hajime
脂肪母细胞瘤是儿童中一种生长迅速的良性肿瘤。手术切除通常可以治愈，复发率约为20%。由于脂肪母细胞瘤的组织学具有异质性，并与其他脂肪瘤性肿瘤有重叠，一些脂肪母细胞瘤病例难以诊断。PLAG1基因重排的检测对脂肪母细胞瘤的诊断有重要意义。在脂肪母细胞瘤中，已知有三个融合伴侣基因与PLAG1有关，HAS2在8q24.1， COL1A2在7q22， RAD51L1在14q24。在此，我们描述了另外两个新的融合基因在脂肪母细胞瘤肿瘤标本。我们检查了6个肿瘤中存在两种已知的融合基因，HAS2-PLAG1和COL1A2-PLAG1。其中一例仅检出HAS2-PLAG1。接下来，我们尝试使用5'RACE识别潜在的PLAG1融合伙伴。序列分析发现了2个新的融合基因，COL3A1-PLAG1 3例，RAB2A-PLAG1 1例。易位的结果是，伴侣基因的本构激活启动子驱动PLAG1的异位表达。我们还评估了PLAG1的高水平表达是否可以用于帮助区分脂肪瘤性肿瘤。实时荧光定量PCR检测5例脂肪母细胞瘤标本中PLAG1的表达。脂肪母细胞瘤的表达量是人脂肪细胞的70-150倍。而PLAG1在1例脂肪瘤中表达较低。这些结果表明，PLAG1过表达是脂肪母细胞瘤的潜在标志物。我们的发现与以往的研究一致，表明脂肪母细胞瘤是一组PLAG1重排和过表达的脂肪瘤性肿瘤。(c) 2014 Wiley期刊公司
Lipoblastoma is a rapidly growing, benign neoplasm in children. Surgical excision is usually curative, with a recurrence rate of about 20%. Because the histology of lipoblastoma is heterogeneous and overlaps with other lipomatous tumors, some lipoblastoma cases have been difficult to diagnose. The detection of PLAG1 gene rearrangement is useful for the diagnosis of lipoblastoma. Three fusion partner genes are known in relation to PLAG1 in lipoblastoma HAS2 at 8q24.1, COL1A2 at 7q22, and RAD51L1 at 14q24. Herein, we describe another two novel fusion genes in lipoblastoma tumor specimens. We checked six tumors for the presence of two known fusion genes, HAS2-PLAG1 and COL1A2-PLAG1. Only HAS2-PLAG1 was found in one of the cases. Next, we attempted to identify potential PLAG1 fusion partners using 5'RACE. Sequence analysis revealed two novel fusion genes, COL3A1-PLAG1 in three cases and RAB2A-PLAG1 in one case, respectively. As a result of the translocations, the constitutively active promoter of the partner gene drives the ectopic expression of PLAG1. We also evaluated whether a high level of PLAG1 expression can be used to help differentiate lipomatous tumors. PLAG1 expression was evaluated by real-time PCR in five lipoblastoma tumor specimens. The expressions were 70-150 times higher in lipoblastomas than in human adipocytes. However, PLAG1 expression was low in one case of lipoma. These results demonstrate that PLAG1 overexpression is a potential marker of lipoblastoma. Our findings, in agreement with previous studies, show that lipoblastoma is a group of lipomatous tumors with PLAG1 rearrangement and overexpression. (c) 2014 Wiley Periodicals, Inc.