Lipomatous solitary fibrous tumors harbor rare NAB2-STAT6 fusion variants and show upregulation of the gene Peroxisome Proliferator Activated Receptor Gamma (PPARG) encoding for a regulator of adipocyte differentiation.

Abstract Solitary fibrous tumors (SFTs) harbor activating NAB2-STAT6 gene fusions. Different variants of the NAB2-STAT6 gene fusion have been associated with distinct clinico-pathological features. Lipomatous SFTs are a morphological variant of SFTs characterized by a fat-forming tumor component. The aim of the current study was to evaluate NAB2-STAT6 fusion variants and further molecular genetic features in a cohort of lipomatous SFTs. A hybrid-capture based next-generation sequencing panel was employed to detect NAB2-STAT6 gene fusions at the RNA level. Additionally, the RNA expression levels of 507 genes were evaluated using this panel, and were compared to a control cohort of non-lipomatous SFTs. Notably, 5/11 (45%) of lipomatous SFTs in the current series harbored the uncommon NAB2 exon 4 - STAT6 exon 4 gene fusion variant, which is observed in only 0.9 – 1.4% of non-lipomatous SFTs. Furthermore, lipomatous SFTs displayed significant differences in gene expression compared to their non-lipomatous counterparts, including upregulation of the gene Peroxisome Proliferator Activated Receptor Gamma (PPARG). PPARγ is a nuclear receptor regulating adipocyte differentiation, providing a possible explanation for the fat-forming component in lipomatous SFTs. In summary, the current study provides a possible molecular genetic basis for the distinct morphological features of lipomatous SFTs.