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DNA copy number changes in childhood acute lymphoblastic leukemia
M L Larramendy1, T Huhta, K Heinonen
1Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
Background And Objective:
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.
Design And Methods:
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.
Results:
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%).
Interpretation And Conclusions:
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.