Abstract
Anaplastic large cell lymphomas (ALCL) in children represent a heterogeneous group of neoplasms with regard to the cell lineages involved. The chromosomal 5q35 breakpoint (bp) and the expression of the NPM/ ALK fusion gene are the most remarkable molecular cytogenetic features of these malignancies. To identify new locations of ALCL-related oncogenes, comparative genomic hybridization (CGH) was applied to three ALCL cell lines (SU-DHL-1, Karpas 299, and DEL) exhibiting the 5q35 bp and expressing the NPM/ ALK transcript. The CGH profiles were compared with those obtained with DNA from U937, HL-60 cells, and altered lymph nodes from two children with ALCL. Significant DNA copy number gains and/or losses were observed on several chromosomes in all ALCL cell lines. Distinct amplicons were detected on 1q21∼q44 (DEL), 7q12 (SU-DHL-1), and 1q12∼q22 (Karpas 299) regions. The NPM/ ALK fusion gene was confirmed by fluorescence in situ hybridization (FISH) analysis in more than 80% of interphase nuclei and metaphase spreads. Enhanced expression of TGF-β2 and c- MET candidate genes located at the amplified regions was revealed in DEL and SU-DHL1 cell lines by Northern blot analysis. These findings delineate chromosomal imbalances in ALCL-derived cell lines in parallel with high level of amplification covering target DNA sequences, which could play a role in ALCL pathogenesis.
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