| Written | 2014-12 | Charles Walther, Fredrik Mertens |
| Department of Pathology, University, Regional Laboratories, Skne University Hospital, 221 85 Lund, Charles.walther@med.lu.se (CW; Department of Clinical Genetics, University, Regional Laboratories, Skne University Hospital, Lund University, 221 85 Lund, Fredrik.Mertens@med.lu.se (FM)Sweden |
| Abstract |
| Abstract | Pseudomyogenic hemangioendothelioma (PHE) is an intermediate malignant vascular tumor primarily affecting soft tissues in children and young adults. The molecular basis of this neoplasm is unknown. Chromosome banding analysis, fluorescence in situ hybridization (FISH), mRNA sequencing, RT-PCR, and quantitative real-time PCR have shown that PHEs are characterized by a balanced translocation t(7;19)(q22;q13), resulting in the fusion of the SERPINE1 and FOSB genes. The role of SERPINE1, which is highly expressed in vascular cells, in this gene fusion is probably to provide a strong promoter for FOSB. 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. |
| Identity |
| Atlas_Id | 6473 |
| Phylum | Soft Tissues::Hemangioendothelioma |
| Other names | Epitheloid sarcoma-like hemangioendothelioma |
| Clinics and Pathology |
| Note | Newly recognised entity. Rare. Exact incidence not known. |
| Etiology | Not known. |
| Epidemiology | Often young adults. Predominantly male (4.6:1) |
| Clinics | Two thirds of the lesions seen in limbs followed by trunk and head and neck. Size 0.3-5.5 cm. Often multifocal and ill circumscribed. Situated subcutanously but often in different tissue planes, including bone. Painful nodules in 50% of the cases. Locally aggressive and often recurring but rarely distant metastases. (Hornick et al., 2011) |
| Pathology | Spindle cells in fascicles and sheets. Vesicular nuclei. Distinct eosinophilic cytoplasm. Cells often show a rhabdomyoblast-like appearance. |
| Treatment | Surgical resection |
| Genetics |
| Note | PHE consistently displays a SERPINE1-FOSB fusion gene, resulting from a translocation between chromosomes 7 and 19, presumably constituting the essential driver mutation in this neoplasm (Trombetta et al., 2011). |
| Cytogenetics |
| Cytogenetics Morphological | a recurrent translocation t(7;19)(q22;q13) has been seen. |
 | |
| Interphase FISH with BAC probes showing normal red (SERPINE1) and green (FOSB) signals and yellow fusion (SERPINE1-FOSB) signal. | |
| Genes involved and Proteins |
| Note | SERPINE1 and FOSB |
| Gene Name | SERPINE1 |
| Location | 7q22.1; chr7:100,770,370-100,782,547 |
| Dna / Rna | 12,178 nt |
| Protein | SERPINE1 (aka PAI-1, plasminogen activator inhibitor type 1) encodes a protein that is a member of the serine protease inhibitor family, and that inhibits tissue- and urokinase-type plasminogen activators. These activators convert plasminogen to plasmin, which in turn mediates fibrinolysis and proteolytic degradation of extracellular matrix. It is highly expressed in many tumors, being implicated in invasion, angiogenesis and metastasis (Declerck et al., 2013). |
| Gene Name | FOSB |
| Location | 19q13.32; chr19:45,971,253-45,978,437 |
| Dna / Rna | 7,185 nt |
| Protein | Member of FOS family of genes, which code for leucine zipper proteins that act as transcription factors. FOSB consists of 338 amino acids (aa), with a central basic leucine-zipper region and a carboxy-terminal transactivation domain (TAD) (Milde-Langosh, 2005). |
| Result of the chromosomal anomaly |
| Hybrid Gene | |
 | |
| Chromatogram showing the fusion junction in a case of PHE. Sixty-one nucleotides from intron 1 of SERPINE1 were inserted at the fusion junction (blue double arrow). The translation start codon in FOSB is indicated (black arrow). | |
| Transcript | RT-PCR and subsequent sequencing of amplified products from two cases identified an in-frame SERPINE-/FOSB fusion transcripts in both cases. In both tumors the breakpoints in SERPINE1 were located in the non-coding exon 1. 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). |
| Fusion Protein | |
| Oncogenesis | The role of SERPINE1 in the SERPINE1-FOSB chimera is probably to provide a promoter allowing strong expression of FOSB. |
| Bibliography |
| Three decades of research on plasminogen activator inhibitor-1: a multifaceted serpin |
| Declerck PJ, Gils A |
| Semin Thromb Hemost 2013 Jun;39(4):356-64 |
| PMID 23504606 |
| Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior |
| Hornick JL, Fletcher CD |
| Am J Surg Pathol 2011 Feb;35(2):190-201 |
| PMID 21263239 |
| The Fos family of transcription factors and their role in tumourigenesis |
| Milde-Langosch K |
| Eur J Cancer 2005 Nov;41(16):2449-61 |
| PMID 16199154 |
| Translocation t(7;19)(q22;q13) recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? Cancer Genet |
| Trombetta D, Magnusson L, von Steyern FV, Hornick JL, Fletcher CD, Mertens F |
| 2011 Apr;204(4):211-5 doi: 10 |
| PMID 21536240 |
| A novel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic haemangioendothelioma |
| Walther C, Tayebwa J, Lilljebjörn H, Magnusson L, Nilsson J, von Steyern FV, Øra I, Domanski HA, Fioretos T, Nord KH, Fletcher CD, Mertens F |
| J Pathol 2014 Apr;232(5):534-40 |
| PMID 24374978 |
| Citation |
| This paper should be referenced as such : |
| Walther C, Mertens F |
| Pseudomyogenic hemangioendothelioma: t(7;19)(q22;q13) SERPINE1/FOS |
| Atlas Genet Cytogenet Oncol Haematol. in press |
| On line version : http://AtlasGeneticsOncology.org/Tumors/PHEt0719q22q13ID6473.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(7;19)(q22;q13) SERPINE1/FOSB | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:25:07 CEST 2017 |
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