Fusion events lead to truncation of FOS in epithelioid hemangioma of bone

David G P van Ijzendoorn, Danielle de Jong, Cleofe Romagosa, Piero Picci, Maria Serena Benassi, Marco Gambarotti, Soeren Daugaard, Michiel van de Sande, Karoly Szuhai, Judith V M G Bovée

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelioid hemangioma of bone is a locally aggressive vascular neoplasm. It can be challenging to diagnose because of the wide histological spectrum, which can make it difficult to differentiate from other vascular neoplasms such as epithelioid hemangioendothelioma or epithelioid angiosarcoma. COBRA-FISH karyotyping identified a balanced t(3;14) translocation. Transcriptome sequencing of the index case and two other epithelioid hemangiomas revealed a recurrent translocation breakpoint involving the FOS gene, which was fused to different partners in all three cases. The break was observed in exon 4 of the FOS gene and the fusion event led to the introduction of a stop codon. In all instances, the truncation of the FOS gene would result in the loss of the transactivation domain (TAD). Using FISH probes we found a break in the FOS gene in two additional cases, in none of these cases a recurrent fusion partner could be identified. In total, FOS was split in 5/7 evaluable samples. We did not observe point mutations leading to early stop codons in any of the 10 cases where RNA was available. Detection of FOS rearrangement may be a useful diagnostic tool to assist in the often difficult differential diagnosis of vascular tumors of bone. Our data suggest that the translocation causes truncation of the FOS protein, with loss of the TAD, which is thereby a novel mechanism involved in tumorigenesis.

Original languageEnglish
Pages (from-to)565-574
Number of pages10
JournalGenes Chromosomes and Cancer
Volume54
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Fingerprint Dive into the research topics of 'Fusion events lead to truncation of FOS in epithelioid hemangioma of bone'. Together they form a unique fingerprint.

Cite this