Clonal Heterogeneity in Patients with Myelodysplastic Syndromes (MDS) and Complex Karyotypes
Introduction: Complex chromosomal aberrations (CCAs) are seen in approximately 20% of patients with newly-diagnosed MDS and are associated with poor prognosis. Bone marrow cells of MDS patients with CCAs are characterized by a high degree of genomic instability, which is connected with an increased...
Saved in:
| Published in: | Blood 2014-12, Vol.124 (21), p.859-859 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Introduction: Complex chromosomal aberrations (CCAs) are seen in approximately 20% of patients with newly-diagnosed MDS and are associated with poor prognosis. Bone marrow cells of MDS patients with CCAs are characterized by a high degree of genomic instability, which is connected with an increased risk of formation of different subclones with additional aberrations. The phenomenon of clonal evolution can be observed either at diagnosis or during the disease progression. At diagnosis it is manifested by the presence of two or more related subclones derived from one founder clone. These subclones can obtain a proliferative advantage leading to the clonal expansion. The aim of the study was to perform detailed genome-wide analyses of bone marrow cells of previously untreated MDS patients with CCAs, to investigate the clonal heterogeneity and to assess the frequency and clinical significance of related cytogenetic subclones with complex karyotypes.
Methods: A comprehensive molecular cytogenetic analysis of fixed bone-marrow cells from 182 adults with CCAs (³3 aberrations) identified with conventional G-banding in the diagnosis of MDS was performed. The CCAs were studied through FISH with Vysis DNA probes (Abbott, Des Plaines, IL) and mFISH/mBAND methods (MetaSystems, Altlussheim, Germany). Genomic imbalances were identified with CytoChip Cancer SNP 180K (BlueGnome, Cambridge, UK) or with Illumina Human CytoSNP-12 arrays (Illumina, San Diego, CA).
Results: Cytogenetic subclones were detected in 143 of 183 patients with complex karyotypes (78.6%). Among them, 98/183 cases (53.8%) displayed a defined number of subclones, whereas in 45/183 patients (24.7%) a precise definition of the individual subclones was not possible due to the high number of heterogeneous findings. Therefore these patients were subsumed as having composite karyotype. In 138/143 cases with clonal heterogeneity (94.9%) subclones showed related karyotypes. Twelve patients had one clone with an interstitial 5q deletion as the sole abnormality and other subclones with additional changes. One of these 12 cases displayed a subclone with complex karyotype in which deleted chromosome 5 was involved in an unbalanced translocation. Five patients (5.1%) had a combination of related clones with del(5q) and additional changes and unrelated subclones without this aberration. Complex aberrations were often associated with the loss of heterozygosity (LOH) of 17p (44%), however a difference in the frequency o |
|---|---|
| ISSN: | 0006-4971 1528-0020 |