title: A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias.
abstract: Chromosomal translocations with breakpoints in T-cell receptor (TCR) genes are recurrent in T-cell malignancies. These translocations involve the TCRalphadelta gene (14q11), the TCRbeta gene (7q34) and to a lesser extent the TCRgamma gene at chromosomal band 7p14 and juxtapose T-cell oncogenes next to TCR regulatory sequences leading to deregulated expression of those oncogenes. Here, we describe a new recurrent chromosomal inversion of chromosome 7, inv(7)(p15q34), in a subset of patients with T-cell acute lymphoblastic leukemia characterized by CD2 negative and CD4 positive, CD8 negative blasts. This rearrangement juxtaposes the distal part of the HOXA gene cluster on 7p15 to the TCRbeta locus on 7q34. Real time quantitative PCR analysis for all HOXA genes revealed high levels of HOXA10 and HOXA11 expression in all inv(7) positive cases. This is the first report of a recurrent chromosome rearrangement targeting the HOXA gene cluster in T-cell malignancies resulting in deregulated HOXA gene expression (particularly HOXA10 and HOXA11) and is in keeping with a previous report suggesting HOXA deregulation in MLL-rearranged T- and B cell lymphoblastic leukemia as the key factor in leukaemic transformation. Finally, our observation also supports the previous suggested role of HOXA10 and HOXA11 in normal thymocyte development.
authors.affiliation: Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium. franki.speleman@ugent.be
authors.forename: F
authors.initials: F
authors.lastname: Speleman
authors.forename: B
authors.initials: B
authors.lastname: Cauwelier
authors.forename: N
authors.initials: N
authors.lastname: Dastugue
authors.forename: J
authors.initials: J
authors.lastname: Cools
authors.forename: B
authors.initials: B
authors.lastname: Verhasselt
authors.forename: B
authors.initials: B
authors.lastname: Poppe
authors.forename: N
authors.initials: N
authors.lastname: Van Roy
authors.forename: J
authors.initials: J
authors.lastname: Vandesompele
authors.forename: C
authors.initials: C
authors.lastname: Graux
authors.forename: A
authors.initials: A
authors.lastname: Uyttebroeck
authors.forename: M
authors.initials: M
authors.lastname: Boogaerts
authors.forename: B
authors.initials: B
authors.lastname: De Moerloose
authors.forename: Y
authors.initials: Y
authors.lastname: Benoit
authors.forename: D
authors.initials: D
authors.lastname: Selleslag
authors.forename: J
authors.initials: J
authors.lastname: Billiet
authors.forename: A
authors.initials: A
authors.lastname: Robert
authors.forename: F
authors.initials: F
authors.lastname: Huguet
authors.forename: P
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: A
authors.initials: A
authors.lastname: De Paepe
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D007446:Chromosome Inversion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020732:Cytogenetic Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015533:Transcriptional Activation / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C484298:HOXA11 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C069634:HOXA10 protein, human