19110b81d474c33abdff206d25e85cc3 271890.pdf 7b83d8fbed1a783b58cb29a750261fc5b88bebdc 271890.pdf a417ab1823eb6e66402a57856afe9f7e4710a6fae5e9037419f301cc9ca59ac2 271890.pdf Title: A Novel NFIX-STAT6 Gene Fusion in Solitary Fibrous Tumor: A Case Report Subject: Solitary fibrous tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive tumors. The defining genetic driver alteration is the gene fusion NAB2–STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2–STAT6 gene fusion is required for the diagnostic confirmation of solitary fibrous tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated solitary fibrous tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8–STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in solitary fibrous tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity. Keywords: solitary fibrous tumor; gene fusion; STAT6; NFIX–STAT6 Author: David S. Moura, Juan Díaz-Martín, Silvia Bagué, Ruth Orellana-Fernandez, Ana Sebio, Jose L. Mondaza-Hernandez, Carmen Salguero-Aranda, Federico Rojo, Nadia Hindi, Christopher D. M. Fletcher and Javier Martin-Broto Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jul 21 05:50:57 2021 CEST ModDate: Wed Jul 21 05:55:52 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2520232 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- RAHZLH+URWPalladioL-Ital Type 1 Custom yes yes no 10 0 CLYRYD+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 OHTCRC+URWPalladioL-BoldItal Type 1 Custom yes yes no 19 0 XNWSMG+URWPalladioL-Roma Type 1 Custom yes yes no 23 0 YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 27 0 OPZDHV+VnURWPalladioL Type 1 Custom yes yes no 32 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 40 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 43 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 65 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 69 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 73 0 MMNAIC+CMSY10 Type 1 Builtin yes yes no 88 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 03:04:41 CEST RepresentationInformation: 271890.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:05:10 CEST Size: 2520232 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 237 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Clinical and Pathological Features Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Fusion Description Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Material and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Targeted RNA-Seq Library Preparation and Sequencing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: RT-PCR and Sanger Sequencing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Immunohistochemistry Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Info: Title: A Novel NFIX-STAT6 Gene Fusion in Solitary Fibrous Tumor: A Case Report Author: David S. Moura, Juan Díaz-Martín, Silvia Bagué, Ruth Orellana-Fernandez, Ana Sebio, Jose L. Mondaza-Hernandez, Carmen Salguero-Aranda, Federico Rojo, Nadia Hindi, Christopher D. M. Fletcher and Javier Martin-Broto Subject: Solitary fibrous tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive tumors. The defining genetic driver alteration is the gene fusion NAB2 STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2 STAT6 gene fusion is required for the diagnostic confirmation of solitary fibrous tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated solitary fibrous tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8 STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in solitary fibrous tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity. 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