Molecular characterization of a complex chromosomal translocation breakpoint t(10;14) including the HOX11 oncogene locus

Abstract

Based on cytogenetic studies, non-random chromosomal translocations which involve the HOX11 gene at locus 10q24 and the TCR genes at loci 7q35 or 14q11 have been reported to occur in 5% of T-ALL. HOX11, a member of the homeobox family of genes, has been shown to play a role in T-ALL. The activation of the HOX11 gene by translocations to the TCR locus results in the inappropriate expression of a 2.3 kb transcript. In this paper we describe a t(10;14)(q24;q11) breakpoint from a T-ALL patient specimen. The breakpoint appears to be mediated by errors in the TCR/V(D)J recombination system, but is more complex than commonly described reciprocal translocations between the HOX11 and TCR genes, since it involves an inversion event of the TCRδ genes. In addition, the breakpoint was characterised to a previously unsequenced area of the 10q24 locus, 3.4 kb upstream of the HOX11 gene. This breakpoint is more centromeric than the breakpoint cluster region previously shown to be involved in the majority of reported t(10;14)(q24;q11) translocations. Hence, our investigations of the translocation breakpoint in this patient identify another breakpoint region in the 10q24 locus and may define a novel recombination ‘hot spot’. Surprisingly, our studies provide a mechanism for a previously unexplained complex translocation described by another group which involves the same region of the HOX11 promoter.