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

Lookup NU author(s): Dr Frederik van Delft, Professor Anthony Moorman, Professor Christine Harrison FRCPath FMedSci

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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.


Publication metadata

Author(s): Strefford JC, Worley H, Barber K, Wright S, Stewart ARM, Robinson HM, Bettney G, van Delft FW, Atherton MG, Davies T, Griffiths M, Hing S, Ross FM, Talley P, Saha V, Moorman AV, Harrison CJ

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2007

Volume: 26

Issue: 29

Pages: 4306-4318

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594

URL: http://dx.doi.org/10.1038/sj.onc.1210190

DOI: 10.1038/sj.onc.1210190

Notes: Comparative Study Journal Article Research Support, Non-U.S. Gov't England


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