The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1

Helen Parker, Qian An, Kerry Barber, Marian Case, Teresa Davies, Zoë Konn, Adam Stewart, Sarah Wright, Mike Griffiths, Fiona M. Ross, Anthony V. Moorman, Andy G. Hall, Julie A. Irving, Christine J. Harrison, Jon C. Strefford

Research output: Contribution to journalArticle

Abstract

The ETV6-RUNX1 fusion is the molecular consequence of the t(12;21)(p13;q22) seen in ∼25% of children with acute lymphoblastic leukemia (ALL). Studies have shown that the fusion alone is insufficient for the initiation of leukemia; additional genetic changes are required. Genomic profiling identified copy number alterations at high frequencies in these patients. Focal deletions of TBL1XR1 were observed in 15% of cases; 3 patients exhibited deletions distal to the gene. Fluorescence in situ hybridization confirmed these deletions and quantitative RT-PCR showed that the TBL1XR1 gene was significantly underexpressed. TBL1XR1 is a key component of the SMRT and N-CoR compressor complexes, which control hormone-receptor mediated gene expression. Differential expression of the retinoic acid target genes, RARB, CRABP1, and CRABP2, indicated that deletion of TBL1XR1 compromised the function of SMRT/N-CoR in the appropriate control of gene expression. This study identifies deletions of TBL1XR1 as a recurrent abnormality in ETV6-RUNX1 positive ALL. We provide evidence that implicates this deletion in the inappropriate control of gene expression in these patients. The target of the interaction between TBL1XR1 and the signaling pathways described here may be exploited in cancer therapy.

Original languageEnglish (US)
Pages (from-to)1118-1125
Number of pages8
JournalGenes Chromosomes and Cancer
Volume47
Issue number12
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1'. Together they form a unique fingerprint.

  • Cite this

    Parker, H., An, Q., Barber, K., Case, M., Davies, T., Konn, Z., Stewart, A., Wright, S., Griffiths, M., Ross, F. M., Moorman, A. V., Hall, A. G., Irving, J. A., Harrison, C. J., & Strefford, J. C. (2008). The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1. Genes Chromosomes and Cancer, 47(12), 1118-1125. https://doi.org/10.1002/gcc.20613