Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes (IPC), UMR1068 Inserm, Marseille, France.
PLoS One. 2013 May 29;8(5):e64497. doi: 10.1371/journal.pone.0064497. Print 2013.
Solitary fibrous tumors (SFTs) are rare spindle-cell tumors. Their cell-of-origin and molecular basis are poorly known. They raise several clinical problems. Differential diagnosis may be difficult, prognosis is poorly apprehended by histoclinical features, and no effective therapy exists for advanced stages.
We profiled 16 SFT samples using whole-genome DNA microarrays and analyzed their expression profiles with publicly available profiles of 36 additional SFTs and 212 soft tissue sarcomas (STSs). Immunohistochemistry was applied to validate the expression of some discriminating genes.
SFTs displayed whole-genome expression profiles more homogeneous and different from STSs, but closer to genetically-simple than genetically-complex STSs. The SFTs/STSs comparison identified a high percentage (∼30%) of genes as differentially expressed, most of them without any DNA copy number alteration. One of the genes most overexpressed in SFTs encoded the ALDH1 stem cell marker. Several upregulated genes and associated ontologies were also related to progenitor/stem cells. SFTs also overexpressed genes encoding therapeutic targets such as kinases (EGFR, ERBB2, FGFR1, JAK2), histone deacetylases, or retinoic acid receptors. Their overexpression was found in all SFTs, regardless the anatomical location. Finally, we identified a 31-gene signature associated with the mitotic count, containing many genes related to cell cycle/mitosis, including AURKA.
We established a robust repertoire of genes differentially expressed in SFTs. Certain overexpressed genes could provide new diagnostic (ALDH1A1), prognostic (AURKA) and/or therapeutic targets.
孤立性纤维瘤（SFT）是一种罕见的梭形细胞肿瘤。其起源细胞和分子基础知之甚少。它们引发了一些临床问题。鉴别诊断可能具有挑战性，组织学特征对预后的理解较差，并且对于晚期阶段尚无有效的治疗方法。
我们使用全基因组 DNA 微阵列对 16 个 SFT 样本进行了分析，并通过公开的 36 个其他 SFT 和 212 个软组织肉瘤（STS）的表达谱分析了它们的表达谱。应用免疫组织化学来验证一些有区别的基因的表达。
SFT 显示出更同质且与 STS 不同的全基因组表达谱，但与遗传简单的 STS 相比更接近遗传复杂的 STS。SFT/STS 比较鉴定出约 30％的基因表达差异，其中大多数没有任何 DNA 拷贝数改变。在 SFT 中过度表达的基因之一编码 ALDH1 干细胞标志物。一些上调的基因和相关的本体论也与祖细胞/干细胞有关。SFT 还过度表达了编码治疗靶标的基因，如激酶（EGFR、ERBB2、FGFR1、JAK2）、组蛋白去乙酰化酶或视黄酸受体。无论解剖位置如何，它们都过度表达。最后，我们确定了与有丝分裂计数相关的 31 个基因特征，其中包含许多与细胞周期/有丝分裂相关的基因，包括 AURKA。
我们建立了 SFT 中差异表达的基因的可靠谱。某些过表达的基因可以提供新的诊断（ALDH1A1）、预后（AURKA）和/或治疗靶标。
