2012
DOI: 10.1038/leu.2012.13
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Quantification of subclonal distributions of recurrent genomic aberrations in paired pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia

Abstract: Genome-wide array approaches and sequencing analyses are powerful tools for identifying genetic aberrations in cancers, including leukemias and lymphomas. However, the clinical and biological significance of such aberrations and their subclonal distribution are poorly understood. Here, we present the first genome-wide array based study of pre-treatment and relapse samples from patients with B-cell chronic lymphocytic leukemia (B-CLL) that uses the computational statistical tool OncoSNP. We show that quantifica… Show more

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Cited by 64 publications
(64 citation statements)
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References 47 publications
(54 reference statements)
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“…3,9,18,39 Using our targeted NGS approach on bulk leukemia cells, the likely subclonal distribution of the MH profile could only be inferred. Longitudinal genome-wide studies including multiple time points or single cell approaches are required to precisely reconstruct the tumor phylogeny.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…3,9,18,39 Using our targeted NGS approach on bulk leukemia cells, the likely subclonal distribution of the MH profile could only be inferred. Longitudinal genome-wide studies including multiple time points or single cell approaches are required to precisely reconstruct the tumor phylogeny.…”
Section: Discussionmentioning
confidence: 99%
“…However, there is evidence from previous whole genome array studies that there is a strong correlation between genomic complexity and the presence of TP53 disruption. 39,40 Therefore, large patient cohorts will be required to unravel potential independence of these phenomena.…”
Section: Discussionmentioning
confidence: 99%
“…It is not known at the moment whether the mutation order is important for the clinical course but similar to clonal, subclonal mutations may carry prognostic value [35]. Integrating genomic data from sequential samples, three types of CLL evolution were identified, which associate with patient's course: (i) no evolution, (ii) linear evolution, and (iii) branched evolution [9,11,26,[129][130][131][132]. Branched evolution is associated with disease evolution and dismal prognosis, probably because the generated genetic diversity allows for a more efficient selection of fitted cells.…”
Section: Intrapatient Heterogeneitymentioning
confidence: 99%
“…Using conventional prognostic markers, all 3 patients belonged to an intermediate risk group (IgVH unmutated, no TP53 abnormalities, no genomic complexity [32][33][34][35][36] ; supplemental Table 1) and were treated with similar combinations of alkylating agents, purine analogues, and immunotherapy.…”
Section: Patterns Of Clonal Evolution Are Heterogeneous In Cllmentioning
confidence: 99%