Abstract
Chromosomal abnormalities are important for the classification and risk stratification of patients with acute lymphoblastic leukemia (ALL). However, approximately 30% of childhood and 50% of adult patients lack abnormalities with clinical relevance. Here, we describe the use of array-based comparative genomic hybridization (aCGH) to identify copy number alterations (CNA) in 58 ALL patients. CNA were identified in 83% of cases, and most frequently involved chromosomes 21 (n=42), 9 (n=21), 6 (n=16), 12 (n=11), 15 (n=11), 8 (n=10) and 17 (n=10). Deletions of 6q (del(6q)) were heterogeneous in size, in agreement with previous data, demonstrating the sensitivity of aCGH to measure CNA. Although 9p deletions showed considerable variability in both the extent and location, all encompassed the CDKN2A locus. Six patients showed del(12p), with a common region encompassing the ETV6 gene. Complex CNA were observed involving chromosomes 6 (n=2), 15 (n=2) and 21 (n=11) with multiple regions of loss and gain along each chromosome. Chromosome 21 CNA shared a common region of gain, with associated subtelomeric deletions. Other recurrent findings included dim(13q), dim(16q) and enh(17q). This is the first report of genome-wide detection of CNA in ALL patients using aCGH, and it has demonstrated a higher level of karyotype complexity than anticipated from conventional cytogenetic analysis.
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Acknowledgements
This study could not have been performed without the dedication of the MRC Childhood and Adult Leukaemia Working Parties and their members, who have designed and coordinated the clinical trials through which these patients were identified and treated. We thank the UK Cancer Cytogenetics Group laboratories for the contribution of fixed cell suspensions, other members of the Leukaemia Research Cytogenetics Group for technical help and discussion, and Leukaemia Research for financial support.
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Strefford, J., Worley, H., Barber, K. et al. Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization. Oncogene 26, 4306–4318 (2007). https://doi.org/10.1038/sj.onc.1210190
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DOI: https://doi.org/10.1038/sj.onc.1210190
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