Molecular changes in solitary fibrous tumor progression

In this study, using 91 SFT cases, we examined whether fusion variants are associated with clinicopathological parameters and also investigated the molecular mechanism of malignant transformation using whole-exome sequencing. We detected variant 1b (NAB2ex4-STAT6ex2) in 51/91 (56%) cases and variants 2a/2b (NAB2ex6-STAT6ex16/17) in 17/91 (19%) cases. TheNAB2-STAT6 fusion variant types were significantly associated with their primary site (P <  0.001). In addition, aTERT promoter mutation was detected in 7/73 (10%) cases, and it showed a significant association with malignant SFTs (P = 0.003). To identify molecular changes during malignant progression, we selected an index patient to obtain parallel tissue samples from the primary and metastatic tumors. In the metastatic tissue, 10 unique molecular alterations, including those inTP53 andAPAF1, were detected. In vitro functional experiments showed thatAPAF1 depletion increased the tumor potency of cells expressing NAB2-STAT6 fusion protein under treatment with staurosporine. We found that TP53 immunopositivity (P = 0.006) and loss of APAF1 immunoreactivity (P <  0.001) were significantly associated with malignant SFTs. Our study suggests that dysfunction ofTP53 andAPAF1 leads to impaired apoptotic function, and eventually contributes toward malignant SFT transformation.Key messagesWe firstly found that theTERT promoter mutation was strongly associated with malignant SFTs (P = 0.003) and the representati...
Source: Journal of Molecular Medicine - Category: Molecular Biology Source Type: research