title: Fusion of ETV6 with an intronic sequence of the BAZ2A gene in a paediatric pre-B acute lymphoblastic leukaemia with a cryptic chromosome 12 rearrangement.
abstract: ETV6 at 12p13 is rearranged in a variety of haematological malignancies and solid tumours, with more than 20 different partners having been reported. These fusions result in either chimeric proteins or activation of the partner gene. However, there are a few examples of abnormalities resulting in truncated and, most likely, unproductive ETV6 proteins, suggesting that haploinsufficiency of ETV6 and/or the partner is leukaemogenic. We present a novel ETV6 rearrangement, identified in a paediatric pre-B acute lymphoblastic leukaemia. Fluorescence in situ hybridisation (FISH) and molecular genetic analyses revealed a fusion of ETV6 and BAZ2A (at 12q13), generated through a cryptic rearrangement between 12p13 and 12q13, consisting of exons 1 and 2 of ETV6 and a sequence from intron 1 of BAZ2A. This transcript is not expected to produce any chimeric protein, but may encode a truncated form of ETV6, containing the first 54 amino acids (aa), followed by 16 aa from the 3' fusion sequence, reminiscent of ETV6 fusions with MDS2, LOC115548, PER1, and STL. The rearrangement might also modify the regulation of BAZ2A by either activating a cryptic promoter or by coming under the control of the ETV6 promoter. The present case emphasises that 'unproductive' ETV6 rearrangements may play an important pathogenetic role in leukaemia.
authors.affiliation: Department of Clinical Genetics, Lund University, University Hospital, Lund, Sweden. ioannis.panagopoulos@med.lu.se
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Bodil
authors.initials: B
authors.lastname: Strömbeck
authors.forename: Margareth
authors.initials: M
authors.lastname: Isaksson
authors.forename: Jesper
authors.initials: J
authors.lastname: Heldrup
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000097764:ETS Translocation Variant 6 Protein; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C436708:BAZ2A protein, human; D000092468:Bromodomain Containing Proteins