Comparative genomic hybridization in childhood acute lymphoblastic leukemia

Abstract

DNA copy number changes were studied by comparative genomic hybridization (CGH) on bone marrow samples obtained from 72 patients with childhood acute lymphoblastic leukemia (ALL) at diagnosis. The patients had been admitted to the Helsinki University Central Hospital (Finland) between 1982 and 1997. CGH showed DNA copy number changes in 45 patients (62.5%) with a mean of 4.6 aberrations per patient (range, 1 to 22). The results of CGH and chromosome banding analysis were generally concordant, but CGH facilitated specific karyotyping in 34 cases. DNA copy number gains were more frequent than losses (gains:losses, 6:1). Gains of DNA sequences affected almost exclusively whole chromosomes and were most commonly observed in chromosomes 21 (25%), 18 (22.2%), X (19.4%), 10 (19.4%) and 17 (19.4%). The most common partial gain was 1q31-q32 (8.3%). The most common gains of chromosomes 21, 18, X, 10, 17, 14, 4, 6 and 8 appeared concurrently. High-level amplifications of small chromosome regions were sporadic, detected only in two patients (2.8%). Chromosome 21 was involved in both cases. The most common losses were 9p22-pter (12.5%) and 12p13-pter (11.1%). No statistically significant association between the CGH findings and the diagnostic white blood cell count was observed.

Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia: recent insights and future directions

“…Array-based comparative genomic hybridization (CGH) using bacterial artificial chromosomes (BACs) has been highly informative in many tumor types, including ALL. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] BAC arrays typically use probes derived from large (up to B200 kb) fragments of human genomic DNA cloned into BAC vectors. BAC arrays now offer tiling coverage of the majority of the human genome, and generally high signal-to-noise ratio, but due to the large probe size have limited ability to detect focal CNA, 36,37 which, as discussed below, are a hallmark of ALL.…”

“…22,23,[25][26][27][28][29][30][31][32][33][34][35]42 These studies have delineated regions of deletion (for example, ETV6 in B-ALL), have mapped translocation breakpoints, 25,30 have identified new CNA (for example, 9q34 duplication in T-ALL), 27 and characterized large and/or complex alterations (for example, gains of 1q and intrachromosomal amplification of chromosome 21 in B-ALL). 26,28 However, the superior resolution of oligonucleotide array platforms, such as SNP arrays, has enabled a more detailed and comprehensive characterization of genetic alterations in ALL.…”

Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas

“…The material consisted of 19 None of the patients had received chemo-or radiotherapy before operation. The histological diagnosis was confirmed by two researchers (TB and VK) by using hematoxylin-eosin (HE) 15 stained slides.…”

“…18 Briefly, tumor DNA and reference DNA (genomic DNA from peripheral blood leukocytes from normal donors) were labelled by nick translation with 19 The hybridization mixture consisted of 400 ng of tumor DNA, 400 ng of reference DNA, and 10 mg of unlabelled human Cot-1 DNA (Gibco/BRL, Life Technologies, Gaithersburg, MD, USA) dissolved in 10 ml of hybridization buffer (50% formamide, 10% dextran sulphate, 2 Â SSC). The hybridization mixture was denatured at 751C for 5 min and hybridized to a slide with normal metaphase spreads denatured in 70% formamide/ 2 Â SSC (pH 7) at 681C for 2 min.…”

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

“…It has identified a number of clinically relevant chromosomal abnormalities (Romana et al, 1994;Berger et al, 2003), and allowed the detection of these alterations in patients with failed cytogenetic results, normal, complex or illdefined karyotypes (Harrison et al, 2005). In spite of its limited resolution, chromosome-based comparative genomic hybridization (cCGH) (Kallioniemi et al, 1992) has provided additional genomic information in some groups of patients (Haas et al, 1998;Larramendy et al, 1998).…”