title: A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42.
abstract: Although many of the chromosomal abnormalities in hematologic malignancies are identifiable cytogenetically, some are only detectable using molecular methods. We describe a novel cryptic t(7;21)(p22;q22) in acute myeloid leukemia (AML). FISH, 3'RACE, and RT-PCR revealed a fusion involving RUNX1 and the ubiquitin-specific protease (USP) gene USP42. The genomic breakpoint was in intron 7 of RUNX1 and intron 1 of USP42. The reciprocal chimera was not detected - neither on the transcriptional nor on the genomic level - and FISH showed that the 5' part of USP42 was deleted. USP42 maps to a 7p22 region characterized by segmental duplications. Notably, 17 kb duplicons are present 1 Mb proximal to USP42 and 3 Mb proximal to RUNX1; these may be important in the genesis of t(7;21). This is the second cryptic RUNX1 translocation in hematologic malignancies and the first in AML. The USPs have not previously been reported to be rearranged in leukemias. The cellular context in which USP42 is active is unknown, but we here show that it is expressed in normal bone marrow, in primary AMLs, and in cancer cell lines. Its involvement in the t(7;21) suggests that deregulation of ubiquitin-associated pathways may be pathogenetically important in AML.
authors.affiliation: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden. kajsa.paulsson@med.lu.se
authors.forename: K
authors.initials: K
authors.lastname: Paulsson
authors.forename: A N
authors.initials: AN
authors.lastname: Békássy
authors.forename: T
authors.initials: T
authors.lastname: Olofsson
authors.forename: F
authors.initials: F
authors.lastname: Mitelman
authors.forename: B
authors.initials: B
authors.lastname: Johansson
authors.forename: I
authors.initials: I
authors.lastname: Panagopoulos
mesh_terms: D000208:Acute Disease; D045744:Cell Line, Tumor; D002648:Child; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D020732:Cytogenetic Analysis / Q000379:methods; D010450:Endopeptidases / Q000235:genetics*; D020869:Gene Expression Profiling; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013869:Thiolester Hydrolases; D014158:Transcription, Genetic; D014178:Translocation, Genetic; D064570:Ubiquitin-Specific Proteases
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C493728:RUNX1 protein, human; C508707:USP42 protein, human; D013869:Thiolester Hydrolases; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases