Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans
Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans
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DOI：
10.1038/modpathol.3800783
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发表时间：
2007-06-01
期刊：
影响因子：
7.5
通讯作者：
Tsuneyoshi, Masazumi
中科院分区：
文献类型：
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作者：
Takahira, Tomonari;Oda, Yoshinao;Tsuneyoshi, Masazumi
在隆突性皮肤纤维肉瘤中已经描述了 I 型胶原蛋白 α1 (COL1A1) 基因与血小板源性生长因子 β 链 (PDGFB) 基因的融合。异常的融合转录本可能导致PDGFB及其受体（血小板源性生长因子受体β，PDGFRB）自分泌刺激和细胞增殖，从而导致隆突性皮肤纤维肉瘤的发生。采用逆转录聚合酶链反应检测 57 个样本中的 COL1A1-PDGFB 融合转录本。此外，对于成功检测到融合转录本的样品，通过实时PCR系统对PDGFB基因扩增和PDGFB/PDGFRB mRNA水平进行定量。在 57 个样本中的 42 个样本中检测到融合转录本。 COL1A1基因的各个外显子与PDGFB基因框内融合；发现外显子 7 和 25 的参与频率略高于其他外显子。 42 个肿瘤样本中的 PDGFB 基因扩增水平从 0.6 到 8.3（平均 2.4）不等，20 个邻近正常组织样本中的 PDGFB 基因扩增水平从 0.4 到 3.0（平均 1.2）不等。在20对样本中，肿瘤中的PDGFB基因扩增明显高于正常组织中的扩增。 26 例中的 26 例和 21 例分别证实了 PDGFB 和 PDGFRB mRNA 的存在。 PDGFB和PDGFRB mRNA表达水平表现出良好的相关性（r = 0.76，P < 0.0001）。这些结果表明，由 COL1A1-PDGFB 转录物加工的融合蛋白可以作为 PDGFRB 的功能配体。
Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene has been described in dermatofibrosarcoma protuberans. The abnormal fusion transcripts probably cause PDGFB and its receptor (platelet-derived growth factor receptor beta, PDGFRB) autocrine stimulation and cell proliferation, which are responsible for the development of dermatofibrosarcoma protuberans. A reverse transcription-polymerase chain reaction assay was performed to detect the COL1A1-PDGFB fusion transcripts in 57 samples. In addition, the PDGFB gene amplification and PDGFB/PDGFRB mRNA levels were quantified by a real-time PCR system for the samples in which the fusion transcripts had been successfully detected. The fusion transcripts were detected in 42 of 57 samples. Various exons of the COL1A1 gene were fused in frame with the PDGFB gene; exons 7 and 25 were found to be slightly more frequently involved than the other exons. The PDGFB gene amplification levels varied from 0.6 to 8.3 (mean 2.4) in 42 tumor samples and from 0.4 to 3.0 (mean 1.2) in 20 adjacent normal tissue samples. In the 20 paired samples, the PDGFB gene amplification in the tumor was significantly higher than that in the normal tissue. The presence of PDGFB and PDGFRB mRNAs was demonstrated in 26 and 21 of 26 cases, respectively. The PDGFB and PDGFRB mRNA expression levels showed a good correlation (r = 0.76, P < 0.0001). These results indicate that the fusion protein, which is processed by the COL1A1-PDGFB transcripts, can serve as a functional ligand for PDGFRB.