Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization

J. C. Strefford, H. Worley, K. Barber, S. Wright, A. R.M. Stewart, H. M. Robinson, G. Bettney, F. W. Van Delft, M. G. Atherton, T. Davies, M. Griffiths, S. Hing, F. M. Ross, P. Talley, V. Saha, A. V. Moorman, C. J. Harrison

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4306-4318
Number of pages13
JournalOncogene
Volume26
Issue number29
DOIs
StatePublished - Jun 21 2007
Externally publishedYes

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Keywords

  • Acute lymphoblastic leukemia
  • Array
  • CGH
  • Copy number

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Strefford, J. C., Worley, H., Barber, K., Wright, S., Stewart, A. R. M., Robinson, H. M., Bettney, G., Van Delft, F. W., Atherton, M. G., Davies, T., Griffiths, M., Hing, S., Ross, F. M., Talley, P., Saha, V., Moorman, A. V., & Harrison, C. J. (2007). Genome complexity in acute lymphoblastic leukemia is revealed by array-based comparative genomic hybridization. Oncogene, 26(29), 4306-4318. https://doi.org/10.1038/sj.onc.1210190