Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma

PLoS One. 2012;7(11):e49705. doi: 10.1371/journal.pone.0049705. Epub 2012 Nov 21.

Abstract

Mesenchymal chondrosarcomas (MCs) account for 3-10% of primary chondrosarcomas. The cytogenetic literature includes only ten such tumours with karyotypic information and no specific aberrations have been identified. Using a purely molecular genetic approach a HEY1-NCOA2 fusion gene was recently detected in 10 of 15 investigated MCs. The fusion probably arises through intrachromosomal rearrangement of chromosome arm 8 q. We report a new case of MC showing a t(1;5)(q42;q32) as the sole karyotypic aberration. Through FISH and whole transcriptome sequencing analysis we found a novel fusion between the IRF2BP2 gene and the transcription factor CDX1 gene arising from the translocation. The IRF2BP2-CDX1 has not formerly been described in human neoplasia. In our hospital's archives three more cases of MC were found, and we examined them looking for the supposedly more common HEY1-NCOA2 fusion, finding it in all three tumours but not in the case showing t(1;5) and IRF2BP2-CDX1 gene fusion. This demonstrates that genetic heterogeneity exists in mesenchymal chondrosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Carrier Proteins / genetics*
  • Child
  • Chondrosarcoma, Mesenchymal / genetics*
  • Chromosome Aberrations
  • Chromosome Banding
  • Chromosomes, Artificial, Bacterial
  • DNA-Binding Proteins
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Middle Aged
  • Models, Genetic
  • Nuclear Proteins / genetics*
  • Transcription Factors
  • Transcriptome*

Substances

  • CDX1 protein, human
  • Carrier Proteins
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • IRF2BP2 protein, human
  • Nuclear Proteins
  • Transcription Factors

Grants and funding

The study was supported by grants from the Norwegian Cancer Society and the South-Eastern Norway Regional Health Authority. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.