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

Int J Mol Sci. 2021 Jul 13;22(14):7514. doi: 10.3390/ijms22147514.

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.

Keywords: NFIX–STAT6; STAT6; gene fusion; solitary fibrous tumor.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Female
  • Gene Fusion*
  • Humans
  • NFI Transcription Factors / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Prognosis
  • STAT6 Transcription Factor / genetics*
  • Solitary Fibrous Tumors / genetics*
  • Solitary Fibrous Tumors / pathology*

Substances

  • NFI Transcription Factors
  • NFIX protein, human
  • Oncogene Proteins, Fusion
  • STAT6 Transcription Factor
  • STAT6 protein, human