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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 quantification of the proportion of copy number alterations (CNAs) and copy neutral loss of heterozygosity regions (cnLOHs) in each sample is feasible. Furthermore, we (i) reveal complex changes in the subclonal architecture of paired samples at relapse compared with pre-treatment, (ii) provide evidence supporting an association between increased genomic complexity and poor clinical outcome (iii) report previously undefined, recurrent CNA/cnLOH regions that expand or newly occur at relapse and therefore might harbor candidate driver genes of relapse and/or chemotherapy resistance. Our findings are likely to impact on future therapeutic strategies aimed towards selecting effective and individually tailored targeted therapies.

Original publication

DOI

10.1038/leu.2012.13

Type

Journal article

Journal

Leukemia

Publication Date

07/2012

Volume

26

Pages

1564 - 1575

Addresses

NIHR Biomedical Research Centre, Oxford, UK.

Keywords

Clone Cells, Humans, Neoplasm Recurrence, Local, Chromosome Aberrations, Prognosis, Oligonucleotide Array Sequence Analysis, Genomics, Gene Dosage, Loss of Heterozygosity, Polymorphism, Single Nucleotide, Genome, Human, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Leukemia, Lymphocytic, Chronic, B-Cell, Biomarkers, Tumor