title: Myeloid leukemia with t(7;21)(p22;q22) and 5q deletion.
abstract: The rare but recurrent RUNX1-USP42 fusion gene is the result of a t(7;21)(p22;q22) chromosomal translocation and has been described in 6 cases of acute myeloid leukemia (AML) and one case of refractory anemia with excess of blast. In the present study, we present the molecular genetic analysis and the clinical features of a t(7;21)(p22;q22)-positive AML case. PCR amplified two RUNX1-USP42 cDNA fragments but no reciprocal USP42-RUNX1 fragment indicating that the RUNX1-USP42 is the leukemogenic fusion gene. Sequencing of the two amplified fragments showed that exon 6 or exon 7 of RUNX1 (accession number NM_001754 version 3) was fused to exon 3 of USP42 (accession number NM_032172 version 2). The predicted RUNX1-USP42 fusion protein would contain the Runt homology domain (RHD), which is responsible for heterodimerization with CBFB and for DNA binding, and the catalytic UCH (ubiquitin carboxyl terminal hydroxylase) domain of the USP42 protein. The bone marrow cells in the present case also had a 5q deletion, and it was revealed that 5 out of the 8 reported cases (including the present case) with t(7;21)(p22;q22)/RUNX1-USP42 also had cytogenetic abnormalities of 5q. The fact that t(7;21) and 5q- occur together much more often than chance would allow seems to be unquestionable, although the pathogenetic connection between the two aberrations remains unknown.
authors.affiliation: Section for Cancer Cytogenetics, Institute for Medical Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. ioannis.panagopoulos@rr-research.no
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gorunova
authors.forename: Petter
authors.initials: P
authors.lastname: Brandal
authors.forename: Margaret
authors.initials: M
authors.lastname: Garnes
authors.forename: Anne
authors.initials: A
authors.lastname: Tierens
authors.forename: Sverre
authors.initials: S
authors.lastname: Heim
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000235:genetics*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*; D013869:Thiolester Hydrolases / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C493728:RUNX1 protein, human; C508707:USP42 protein, human; D013869:Thiolester Hydrolases