title: The Dicentric Chromosome dic(20;22) Is a Recurrent Abnormality in Myelodysplastic Syndromes and Is a Product of Telomere Fusion.
abstract: We describe a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in 4 cases of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). In particular, the presence of residual telomere sequences at the site of translocation in 3 of the 4 cases makes a compelling case for telomere fusion. This is the first description of a recurrent telomere fusion event in any malignant condition. The 20q subtelomeric region was retained in all 4 examples despite deletion of the 20q12 region closer to the centromere. The original dicentric chromosome in all 4 cases contained nucleolus organiser region material from the short arm of chromosome 22 and had also undergone secondary rearrangements that produced amplification of the common gained region on 20q. We propose that the sequence of events producing this chromosome abnormality is: degradation of the telomeres, formation of an unstable dicentric chromosome by 20q and 22p telomere fusion, breakage-fusion-bridge cycles causing copy number aberration between the centromeres, selection of cells with 20q12 deletion, and further selection of cells with 20q11.2 gain. The last 2 steps are driver events responsible for the abnormal chromosomes found in the malignant cells. Finding recurrent patterns in the complex genome reorganisation events that characterise poor-prognosis, complex-karyotype AML and MDS will help us understand the mechanisms and oncogenic driver mutations in these poorly understood malignancies.
authors.affiliation: Victorian Cancer Cytogenetics Service, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Ruth N
authors.initials: RN
authors.lastname: MacKinnon
authors.forename: Hendrika M
authors.initials: HM
authors.lastname: Duivenvoorden
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Campbell
authors.forename: Meaghan
authors.initials: M
authors.lastname: Wall
mesh_terms: D002869:Chromosome Aberrations; D002890:Chromosomes, Human, Pair 20; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016615:Telomere