title: E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3; p13.3) in acute leukemia.
abstract: A 5-year-old boy who initially presented with ALL and relapsed 4 months later with AML was found to have an add(19) in the leukemia cells. FISH revealed that the add(19) was really a cryptic t(l2;l9)(p13.3;p13.3) interrupting E2A (TCF3). Nucleotide sequences of cloned genomic fragments with the E2A rearrangements revealed that the der(12) contained E2A joined to an intron of the NOLI (p120) gene. Reverse transcriptase (RT)-PCR of patient lymphoblast RNA showed expression of in-frame fusion cDNAs consisting of most of NOL1 fused to the 3' portion of E2A that encoded part of the second transcriptional activation domain and the DNA binding and protein dimerization motifs. The reciprocal der(19) E2A genomic rearrangements included 5' regions of E2A joined to an intron of the ZNF384 (NMP4, CIZ) gene, located approximately 450 kb centromeric to NOL1 on chromosome 12. RT-PCR showed expression of in-frame E2A-ZNF384 fusion cDNAs. To our knowledge, this is the second report of a chromosome translocation in leukemia resulting in two different gene fusions. This is the first report of expression of E2A fusion protein that includes the DNA binding and protein dimerization domains due to a more proximal break in E2A compared to those described previously.
authors.affiliation: Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: C-h
authors.initials: CH
authors.lastname: Zhong
authors.forename: V
authors.initials: V
authors.lastname: Prima
authors.forename: X
authors.initials: X
authors.lastname: Liang
authors.forename: C
authors.initials: C
authors.lastname: Frye
authors.forename: L
authors.initials: L
authors.lastname: McGavran
authors.forename: L
authors.initials: L
authors.lastname: Meltesen
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.forename: T
authors.initials: T
authors.lastname: Boomer
authors.forename: M
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: J
authors.initials: J
authors.lastname: Gump
authors.forename: S P
authors.initials: SP
authors.lastname: Hunger
mesh_terms: D000208:Acute Disease; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics*; D001665:Binding Sites; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002888:Chromosomes, Human, Pair 19; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D015321:Gene Rearrangement; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014178:Translocation, Genetic; D012359:tRNA Methyltransferases
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D012359:tRNA Methyltransferases; C407909:TCF3 protein, human; C498621:ZNF384 protein, human; C065028:NOP2 protein, human