A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis

Mol Cancer. 2009 Jan 19;8:5. doi: 10.1186/1476-4598-8-5.

Abstract

Background: The ability to detect neoplasia-specific fusion genes is important not only in cancer research, but also increasingly in clinical settings to ensure that correct diagnosis is made and the optimal treatment is chosen. However, the available methodologies to detect such fusions all have their distinct short-comings.

Results: We describe a novel oligonucleotide microarray strategy whereby one can screen for all known oncogenic fusion transcripts in a single experiment. To accomplish this, we combine measurements of chimeric transcript junctions with exon-wise measurements of individual fusion partners. To demonstrate the usefulness of the approach, we designed a DNA microarray containing 68,861 oligonucleotide probes that includes oligos covering all combinations of chimeric exon-exon junctions from 275 pairs of fusion genes, as well as sets of oligos internal to all the exons of the fusion partners. Using this array, proof of principle was demonstrated by detection of known fusion genes (such as TCF3:PBX1, ETV6:RUNX1, and TMPRSS2:ERG) from all six positive controls consisting of leukemia cell lines and prostate cancer biopsies.

Conclusion: This new method bears promise of an important complement to currently used diagnostic and research tools for the detection of fusion genes in neoplastic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Line, Tumor
  • Core Binding Factor Alpha 2 Subunit / genetics
  • DNA-Binding Proteins / genetics
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis / methods*
  • Oncogene Proteins, Fusion / genetics*
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Prostatic Neoplasms / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ets / genetics
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Serine Endopeptidases / genetics
  • Trans-Activators / genetics
  • Transcriptional Regulator ERG

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Core Binding Factor Alpha 2 Subunit
  • DNA-Binding Proteins
  • ERG protein, human
  • ETS translocation variant 6 protein
  • Oncogene Proteins, Fusion
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RUNX1 protein, human
  • Repressor Proteins
  • TCF3 protein, human
  • Trans-Activators
  • Transcriptional Regulator ERG
  • pbx1 protein, human
  • Serine Endopeptidases
  • TMPRSS2 protein, human