Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines

Cancer cell lines are essential gene discovery tools and have often served as models in genetic and functional studies of particular tumor types. One of the future challenges is comparison and interpretation of gene expressio n data with the available knowledge on the genomic abnormalities in these c ell lines. In this context, accurate description of these genomic abnormali ties is. required. Here, we show that a combination of M-FISH with banding analysis, standard FISH, and CGH allowed a detailed description of the gene tic alterations in 16 neuroblastoma cell lines. In total, 14 cryptic chromo some rearrangements were detected, including a balanced t(2;4)(p2.4.3;q34.3 ) translocation in cell line NBL-S, with the 2p24 breakpoint located at abo ut 40 kb from MYCN. The chromosomal origin of 22 marker chromosomes and 41 cytogenetically undefined translocated segments was determined. Chromosome arm 2 short arm translocations were observed in six cell lines (38%) with a nd five (31%.) without MYCN amplification, leading to partial chromosome ar m 2p gain in all but one cell line and loss of material in the various part ner chromosomes, including 1p and 11q. These 2p gains were often masked in the GGH profiles due to MYCN amplification. The commonly overrepresented re gion was chromosome segment 2pter-2p22, which contains the MYCN gene, and f ive out of eleven 2p breakpoints clustered to the interface of chromosome b ands 2p16 and 2p21. In neuroblastoma cell line SJNB-12, with double minutes (dmins) but no MYCN amplification, the dmins were shown to be derived from 16q22-q23 sequences. The ATBF1 gene, an. AT-binding transcription factor i nvolved in normal neurogenesis and located at 16q22.2, was shown to be pres ent in the amplicon. This is the first report describing the possible impli cation of ATBF1 in neuroblastoma cells. We conclude that a combined approac h of M-FISH, cytogenetics, and CGH allowed a more complete and accurate des cription of the genetic alterations occurring in the investigated cell line s. (C) 2001 Wiley-Liss, Inc.