title: Characterisation of genomic translocation breakpoints and identification of an alternative TCF3/PBX1 fusion transcript in t(1;19)(q23;p13)-positive acute lymphoblastic leukaemias.
abstract: The t(1;19)(q23;p13), one of the most common translocations in childhood and adult acute lymphoblastic leukaemias (ALLs), usually results in fusion of exons 1-16 of TCF3 (previously E2A) and exons 3-9 of PBX1. However, some t(1;19)-positive ALLs are negative for this chimaera. We here report an alternative TCF3/PBX1 transcript, fusing exon 17 of TCF3 with exon 5 of PBX1, in a paediatric t(1;19)-positive ALL. The different breakpoints made this hybrid undetectable by reverse transcription polymerase chain reaction using standard TCF3 and PBX1 primers. Hence, ALLs with t(1;19) that test negative for TCF3/PBX1 should be analysed further before excluding this alternative fusion. Furthermore, we have characterised the genomic translocation breakpoints in eight TCF3/PBX1-positive ALLs; four cases with a balanced t(1;19) and four with an unbalanced der(19)t(1;19). It has previously been suggested that the breakpoints are clustered, particularly in TCF3, and that N-nucleotides are frequently present in the fusion junctions. Three of seven investigated TCF3 intron 16 breakpoints were within the previously described 14 base pair-cluster, and all but two junctions harboured N-nucleotides. The PBX1 breakpoints were more dispersed, although still clustered in two regions. This confirms that most t(1;19) rearrangements may arise by a combination of illegitimate V(D)J recombination and non-homologous end joining.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Paulsson
authors.forename: Tord
authors.initials: T
authors.lastname: Jonson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ora
authors.forename: Tor
authors.initials: T
authors.lastname: Olofsson
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C407909:TCF3 protein, human; C083400:PBX1 protein, human