The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data

På svenska

Author

  • Lu Wang
  • Toru Motoi
  • Raya Khanin
  • Adam Olshen
  • Fredrik Mertens
  • Julia Bridge
  • Paola Dal Cin
  • Cristina R. Antonescu
  • Samuel Singer
  • Meera Hameed
  • Judith V. M. G. Bovee
  • Pancras C. W. Hogendoorn
  • Nicholas Socci
  • Marc Ladanyi
Show all

Summary, in English

Cancer gene fusions that encode a chimeric protein are often characterized by an intragenic discontinuity in the RNA\expression levels of the exons that are 5' or 3' to the fusion point in one or both of the fusion partners due to differences in the levels of activation of their respective promoters. Based on this, we developed an unbiased, genome-wide bioinformatic screen for gene fusions using Affymetrix Exon array expression data. Using a training set of 46 samples with different known gene fusions, we developed a data analysis pipeline, the Fusion Score (FS) model, to score and rank genes for intragenic changes in expression. In a separate discovery set of 41 tumor samples with possible unknown gene fusions, the FS model generated a list of 552 candidate genes. The transcription factor gene NCOA2 was one of the candidates identified in a mesenchymal chondrosarcoma. A novel HEY1-NCOA2 fusion was identified by 5' RACE, representing an in-frame fusion of HEY1 exon 4 to NCOA2 exon 13. RT-PCR or FISH evidence of this HEY1-NCOA2 fusion was present in all additional mesenchymal chondrosarcomas tested with a definitive histologic diagnosis and adequate material for analysis (n = 9) but was absent in 15 samples of other subtypes of chondrosarcomas. We also identified a NUP107-LGR5 fusion in a dedifferentiated liposarcoma but analysis of 17 additional samples did not confirm it as a recurrent event in this sarcoma type. The novel HEY1-NCOA2 fusion appears to be the defining and diagnostic gene fusion in mesenchymal chondrosarcomas. (C) 2011 Wiley Periodicals, Inc.

Department/s

Publishing year

2012

Language

English

Pages

127-139

Publication/Series

Genes, Chromosomes and Cancer

Volume

51

Issue

2

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Medical Genetics

Status

Published

ISBN/ISSN/Other

  • ISSN: 1045-2257