A novel SERPINE1–FOSB fusion gene results in transcriptional up‐regulation of FOSB in pseudomyogenic haemangioendothelioma

Abstract

Pseudomyogenic haemangioendothelioma (PHE) is an intermediate malignant vascular soft tissue tumour primarily affecting children and young adults. The molecular basis of this neoplasm is unknown. We here used chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing, RT-PCR and quantitative real-time PCR on a series of morphologically well-characterized PHEs to show that a balanced translocation, t(7;19)(q22;q13), detected as the sole cytogenetic aberration in two cases, results in fusion of the SERPINE1 and FOSB genes. This translocation has not been observed in any other bone or soft tissue tumour. Interphase FISH on sections from eight additional PHEs identified the same SERPINE1-FOSB fusion in all cases. The role of SERPINE1, which is highly expressed in vascular cells, in this gene fusion is probably to provide a strong promoter for FOSB, which was found to be expressed at higher levels in PHEs than in other soft tissue tumours. FOSB encodes a transcription factor belonging to the FOS family of proteins, which, together with members of the JUN family of transcription factors, are major components of the activating protein 1 (AP-1) complex. Further studies are needed to understand the cellular impact of the aberrant expression of the FOSB gene, but as the t(7;19) resulting in the SERPINE1-FOSB fusion seems to be pathognomonic for PHE, FISH or RT-PCR could be useful for differential diagnostic purposes.

Pseudomyogenic Hemangioendothelioma: A Vascular Tumor Previously Undescribed in the Oral Cavity

“…In a later study, a fusion gene SERPINE1-FOSB resulting from a translocation between chromosomes 7 and 19 was discovered using mRNA sequencing, RT-PCR and interphase FISH analysis [7].…”

Recurrent PRDM10 Gene Fusions in Undifferentiated Pleomorphic Sarcoma

“…RNA-Seq and bioinformatic analysis to identify candidate fusion transcripts were performed on cases 1, 2, 35, 36, 44, and 49. mRNA libraries were prepared for sequencing using the Truseq RNA Sample Preparation Kit v 2 (Illumina) as previously described (12). Briefly, poly-A-tailed RNA was enriched from total RNA using magnetic oligo-dT beads.…”

Pseudomyogenic hemangioendothelioma: t(7;19)(q22;q13) SERPINE1/FOSB

“…The breakpoint in FOSB was located in the beginning of exon 2 in one case and in the non-coding exon 1 in the other. Both cases showed small insertions (61 bp in Case 1, 59 bp in Case 2) of material from intron 1 of SERPINE1 at the fusion junction (Walther et al, 2014).…”