Molecular cytogenetic aberrations in CD30+ anaplastic large cell lymphoma cell lines.
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 approximately q44 (DEL), 7q12 (SU-DHL-1), and 1q12 approximately 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-beta2 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.
Gogusev
Jean
J
INSERM U507, Hôpital Necker, Paris, France. gogusev@necker.fr
Telvi
Louise
L
Nezelof
Christian
C
D015152:Blotting, Northern; D015139:Blotting, Southern; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D017730:Ki-1 Antigen / Q000032:analysis*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017730:Ki-1 Antigen; D012333:RNA, Messenger