title: PAX5 alterations in genetically unclassified childhood Precursor B-cell acute lymphoblastic leukaemia.
abstract: Here, we report a high incidence of PAX5 abnormalities observed in 32/68 (47%) of patients with genetically unclassified childhood precursor B-cell acute lymphoblastic leukaemia (pre-B ALL). Various deletions, gains, mutations and rearrangements of PAX5 comprised 45%, 12%, 29% and 14%, respectively, of the abnormalities found. 28% of patients showed more than one abnormality of the gene, implying bi-allelic impairment of PAX5. Novel PAX5-RHOXF2, PAX5-ELK3 and PAX5-CBFA2T2 rearrangements, which lead to aberrant expression of PAX5, were also identified. PAX5 rearrangements demonstrated a complex mechanism of formation including concurrent duplications/deletions of PAX5 and its partner genes. Finally, the splice variant c.1013-2A>G, seen in two patients with loss of one PAX5 allele, was confirmed to be germ-line in one patient and somatic in the other. PAX5 alterations were also found to be clinically associated with a higher white blood cell count (P = 0·015). These findings contribute to the knowledge of PAX5 alterations and their role in the pathogenesis of pre-B ALL.
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.|Developmental Biology and Cancer (DBC), University College London-Institute of Child Health, London, UK.
authors.forename: Irina
authors.initials: I
authors.lastname: Stasevich
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Inglott
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Austin
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Chatters
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Chalker
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.
authors.forename: Dilys
authors.initials: D
authors.lastname: Addy
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.
authors.forename: Carryl
authors.initials: C
authors.lastname: Dryden
authors.affiliation: Department of Haematology, Great Ormond Street Hospital, London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Ancliff
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ford
authors.affiliation: Developmental Biology and Cancer (DBC), University College London-Institute of Child Health, London, UK.
authors.forename: Owen
authors.initials: O
authors.lastname: Williams
authors.affiliation: Haematology Cellular and Molecular Diagnostic Service, Great Ormond Street Hospital, London, UK.|Developmental Biology and Cancer (DBC), University College London-Institute of Child Health, London, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Kempski
keywords: 
  PAX5
  ; acute lymphoblastic leukaemia; deletions; mutations; rearrangements