A Novel NFIX-STAT6 Gene Fusion in Solitary Fibrous Tumor: A Case Report

Abstract

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.

Lipomatous (Fat-Forming) Solitary Fibrous Tumor of the Breast: A Case Report of an Uncommon Variant of a Rare Clinical Entity

“…The genetic hallmark of SFT is the recurrent gene fusion NAB2-STAT6, located in the chromosomal region 12q13, and involving several different exons in each gene. However, a novel gene fusion, NFIX-STAT6, was identified [ 8 ].…”

STAT6-targeting antisense oligonucleotides against solitary fibrous tumor

“…It should be noted that, although NAB2-STAT6 fusion accounts for almost all known SFT cases, recently we have reported one rare SFT case in which a different fusion type (NFIX-STAT6) was observed. 58 Nevertheless, our current ASO design strategy, which targets the 3′ UTR of STAT6, should also treat those SFT fusions.…”

Solitary fibrous tumor of male breast: A case report and literature review

“…Of the extrapleural SFTs, breast SFT remains the rarest, and histopathological and image diagnosis is both difficult and unsecured. In recent studies, NAB2-STAT6 or NFIX-STAT6 fusion gene was reported to be the driver mutation of SFT, which plays a key role in collagen production, vessel formation, and tumor proliferation [3,4,6] ; however, the IHC staining of preoperative STAT6 staining for breast SFTs are seldom reported, possibly due to its rarity. To our knowledge, 32 cases of breast SFT have been reported in previous case studies (Table S1, http://links.lww.com/MD/ I209).…”