title: Gain of chromosome 21 or amplification of chromosome arm 21q is one mechanism for increased ERG expression in acute myeloid leukemia.
abstract: In acute myeloid leukemia (AML), acquired genomic gains and losses are common and lead to altered expression of genes located within or nearby the affected regions. Increased expression of the ETS-related transcription factor gene ERG has been described in myeloid malignancies with chromosomal rearrangements involving chromosome band 21q22, but also in cytogenetically normal AML, where it is associated with adverse prognosis. In this study, fluorescence in situ hybridization on interphase nuclei disclosed an amplification of the ERG gene (more than six copies) in 33 AML patients with structural rearrangements of 21q22. Array comparative genomic hybridization of these cases disclosed a minimal amplified region at the position 39.6-40.0 Mbp from pter that harbors ERG as the only gene. Analysis by quantitative real-time reverse transcription polymerase chain reaction revealed significantly higher ERG mRNA expression in these patients and in a group of 95 AML patients with complete or partial gain of chromosome 21 (three to six copies) compared with 351 AML patients without gain of chromosome 21. Quantification of ERG DNA copy numbers revealed a strong correlation with ERG mRNA expression. Furthermore, in patients with gain of chromosome 21, higher ERG expression was found to be associated with RUNX1 mutations. Our results suggest that acquired gain of chromosome 21 or amplification of chromosome arm 21q is one mechanism contributing to increased ERG expression in AML.
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Weber
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Jeromin
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Niroshan
authors.initials: N
authors.lastname: Nadarajah
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dicker
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Louisa
authors.initials: L
authors.lastname: Noël
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Zenger
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Alpermann
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.affiliation: MLL Munich Leukemia Laboratory, Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058674:Chromosome Duplication; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C072312:ERG protein, human; C493728:RUNX1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG