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Biotechnical Methods Section (BTS)

Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia


We used a recently described molecular cytogenetic method, spectral karyotyping (SKY), to analyze metaphase chromosomes from 30 pediatric patients with acute lymphoblastic leukemia (ALL). This group included 20 patients whose leukemic blast cells lacked chromosomal abnormalities detected by conventional cytogenetics and 10 patients whose blast cells had multiple chromosomal abnormalities that could not be completely identified by G-banding analysis. In two of the 20 patients (10%) with apparently normal karyotypes, SKY identified three cryptic translocations: a t(7;8)(q34–35;q24.1) in one patient and a t(13;17)(q22;q21) and a der(19)t(17;19)(q22;p13) in another. Fluorescence in situ hybridization using subtelomeric probes proved the latter translocation to be a t(17;19). SKY analysis was also successful in defining the nature of the chromosomal abnormalities in four of the 10 patients with marker and derivative chromosomes. The identified abnormalities in the latter group included three novel translocations: a der(X)t(X;5)(p11.4;q31), a der(21)t(X;21)(p11.4;p11.2) and a t(X;9)(p11.4;p13). The presence of the t(X;9) was suggested by conventional cytogenetics. The application of fluorescence in situ hybridization using chromosome-specific painting probes and locus-specific probes complemented the SKY analysis by confirming the nature of the chromosome rearrangements defined by SKY and by identifying the amplification of the AML1/CBFA2 gene in one patient with a duplicated 21q. Our study demonstrates the utility of SKY in identifying novel translocations and in refining the identity of chromosomal abnormalities in leukemias.

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This work was supported in part by grant CA-20180 and Cancer Center Core grant CA-21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities (ALSAC). We thank Dr RSK Chaganti, Memorial Sloan-Kettering Cancer Center, for allowing us to use the Spectral Karyotyping system during the initial stages of the study. We also thank T O'Neill, P Mardis, E Entrekin, P Dalton, and R Marion for their assistance in the cytogenetic evaluations. We thank Dr JC Jones for editing the manuscript.

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Mathew, S., Rao, P., Dalton, J. et al. Multicolor spectral karyotyping identifies novel translocations in childhood acute lymphoblastic leukemia. Leukemia 15, 468–472 (2001).

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  • novel translocations
  • spectral karyotyping
  • childhood ALL

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