Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
Department of Orthopedics, Karolinska University Hospital, Solna, Sweden.
Clin Cancer Res. 2015 Feb 15;21(4):864-9. doi: 10.1158/1078-0432.CCR-14-2399. Epub 2014 Dec 16.
Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about one third. No tumor-specific rearrangement has been identified, and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions.
RNA-Seq, FISH, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas.
Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3' partner and either MED12 or CITED2 as the 5' partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before.
Our results suggest that PRDM10 fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS.
未分化多形性肉瘤（UPS）被定义为具有细胞多形性且无法识别分化来源的肉瘤。它通常是一种高级别病变，转移率约为三分之一。尚未发现肿瘤特异性重排，也缺乏可用于治疗分层的遗传标志物。我们进行了转录组测序（RNA-Seq）以寻找新的基因融合。
使用 RNA-Seq、荧光原位杂交（FISH）和/或各种 PCR 方法，在 84 例软组织肉瘤中搜索 PRDM10 基因的基因融合和重排。
使用 RNA-Seq，发现两例 UPS 显示出新型基因融合，均涉及转录因子 PRDM10 作为 3' 伙伴，而 MED12 或 CITED2 作为 5' 伙伴基因。对 82 例软组织肉瘤中 PRDM10 基因座的重排进行进一步筛选，发现另一例 UPS 存在 MED12/PRDM10 融合。以前从未有这些基因涉及肿瘤相关基因融合。
我们的结果表明，PRDM10 融合约存在于 5%的 UPS 中。尽管我们系列中融合阳性病例与其他 UPS 具有相同的核多形性和缺乏分化，但值得注意的是，所有三个病例在形态上均为低度恶性，且无患者发生转移。因此，PRDM10 融合阳性肉瘤可能构成 UPS 的一个重要临床亚型。
