title: Molecular characterisation of a recurrent, semi-cryptic RUNX1 translocation t(7;21) in myelodysplastic syndrome and acute myeloid leukaemia.
abstract: A proportion of cytogenetic abnormalities in myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) may escape detection by high-resolution genomic technologies, but can be identified by conventional cytogenetic and molecular analysis. Here, we report the detection of a reciprocal translocation t(7;21)(p22;q22) in the marrow of two adults with MDS and AML, using conventional cytogenetic analysis and fluorescence-in situ-hybridization (FISH). Reverse-transcription polymerase chain reaction (RT-PCR) and sequence analysis identified a fusion between RUNX1 and the gene encoding ubiquitin specific peptidase-42 (USP42), with splice-variants and variable break-points within RUNX1. Combined cytomorphology and FISH studies in MDS marrow revealed abnormal RUNX1 signals within megakaryocytes, suggesting that the acquisition of t(7;21)(p22;q22) does not confer complete differentiation arrest and may represent an early genetic event in leukaemogenesis. Single nucleotide polymorphism-arrays failed to detect additional sub-microscopic genomic changes predisposing to or associated with t(7;21). Molecular analysis of 100 MDS and AML marrow specimens by RT-PCR did not reveal new cases with the RUNX1-USP42 fusion. Thus, our studies have identified t(7;21)(p22;q22) as a rare but recurrent abnormality in MDS/AML, with the existence of alternative spliced forms of the RUNX1-USP42 transcript in different patients. Further studies are required to identify the potential contribution of these splice-variants to disease heterogeneity.
authors.affiliation: Department of Cytogenetics, Ninewells Hospital and Medical School, Dundee, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Foster
authors.forename: Kajsa
authors.initials: K
authors.lastname: Paulsson
authors.forename: Mark
authors.initials: M
authors.lastname: Sales
authors.forename: Joan
authors.initials: J
authors.lastname: Cunningham
authors.forename: Michael
authors.initials: M
authors.lastname: Groves
authors.forename: Nigel
authors.initials: N
authors.lastname: O'Connor
authors.forename: Suriya
authors.initials: S
authors.lastname: Begum
authors.forename: Tracy
authors.initials: T
authors.lastname: Stubbs
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: McMullan
authors.forename: Michael
authors.initials: M
authors.lastname: Griffiths
authors.forename: Norman
authors.initials: N
authors.lastname: Pratt
authors.forename: Sudhir
authors.initials: S
authors.lastname: Tauro
mesh_terms: D000368:Aged; 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*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; C493728:RUNX1 protein, human