Comparative genomic hybridization is a powerful tool, complementary to cytogenetics, to identify chromosomal abnormalities in childhood acute lymphoblastic leukaemia.
ABSTRACT Cytogenetics has a strong prognostic value in childhood acute lymphoblastic leukaemia (ALL), but results are often incomplete because of the poor chromosome morphology. To improve this analysis, we tested comparative genomic hybridization (CGH) for the detection of chromosomal imbalances. 72 children were retrospectively analysed using CGH. Only 53% of the patients had been fully banded by standard methods. With CGH, 36 patients retained a normal chromosomal profile and 36 had unbalanced abnormalities. No amplification was detected. Fluorescence in situ hybridization (FISH) with centromeric and unique sequence probes was used in those cases with discrepancies or unsuccessful karyotype to validate CGH results. CGH enabled clear identification of unbalanced chromosomal abnormalities, even in some cases which had a normal karyotype. In view of the strong prognostic value of hyperdiploidy in childhood ALL, CGH appears to be a powerful technique, complementary to conventional cytogenetics.
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ABSTRACT: Comparative genomic hybridization (CGH) allows the study of DNA copy number changes in a single hybridization from tumor DNA without any cell culture. Three reports of childhood acute lymphoblastic leukemia (ALL) studied by CGH have been published so far, with somewhat discrepant results. In the present study we performed CGH analysis on 36 patients with childhood ALL. The results were compared to those reported earlier on 157 cases. DNA was extracted from bone marrow specimens from 36 patients with childhood ALL. The tumor and reference DNAs were labeled with fluorescein-isothiocyanate conjugated dCTP and dUTP, and Texas red-conjugated dCTP and dUTP. The hybridizations were analyzed using the ISIS digital image analysis system. The most commonly gained chromosomes were X (42%), 4 (31%), 6 (31%), 10 (36%), 14 (28%) and 18 (33%), and the most common losses were at 9p22-pter (6%) and 12p13-pter (14%). The pattern of gains of DNA sequences was very similar in the four reports, but the 9p and 12p deletions were observed only in the present study and one previous report. Our review of the results of 193 patients studied so far shows that the success rate using CGH was close to 100%, whereas cytogenetic analysis failed to reveal any information in 21 patients (11%). Furthermore, in 69 (36%) out of 193 patients CGH gave additional information to the banding analysis. CGH should, therefore, be used to supplement standard cytogenetics in the analysis of childhood ALL patients.Haematologica 11/1998; 83(10):890-5. · 6.42 Impact Factor