title: 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.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Sweden; Department of Pathology, University and Regional Laboratories, Skåne University Hospital, Lund, Sweden.
authors.forename: Charles
authors.initials: C
authors.lastname: Walther
authors.forename: Johnbosco
authors.initials: J
authors.lastname: Tayebwa
authors.forename: Henrik
authors.initials: H
authors.lastname: Lilljebjörn
authors.forename: Linda
authors.initials: L
authors.lastname: Magnusson
authors.forename: Jenny
authors.initials: J
authors.lastname: Nilsson
authors.forename: Fredrik Vult
authors.initials: FV
authors.lastname: von Steyern
authors.forename: Ingrid
authors.initials: I
authors.lastname: Øra
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Thoas
authors.initials: T
authors.lastname: Fioretos
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Nord
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D000293:Adolescent; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002871:Chromosome Banding; D002892:Chromosomes, Human, Pair 22; D002897:Chromosomes, Human, Pair 7; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D050939:Gene Fusion; D005820:Genetic Testing / Q000379:methods; D018323:Hemangioendothelioma, Epithelioid / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011237:Predictive Value of Tests; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D012983:Soft Tissue Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D015854:Up-Regulation
chemical_list: C064269:FOSB protein, human; D017395:Plasminogen Activator Inhibitor 1; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C051321:SERPINE1 protein, human
keywords: FOSB; RNA sequencing; SERPINE1; gene fusion; paediatric; pseudomyogenic haemangioendothelioma; sarcoma