High-resolution analysis of allelic imbalance in neuroblastoma cell lines by single nucleotide polymorphism arrays.
Genomic copy number changes are detectable in many malignancies, including neuroblastoma, using techniques such as comparative genomic hybridization (CGH), microsatellite analysis, conventional karyotyping, and fluorescence in situ hybridization (FISH). We report the use of 10K single nucleotide polymorphism (SNP) microarrays to detect copy number changes and allelic imbalance in six neuroblastoma cell lines (IMR32, SHEP, NBL-S, SJNB-1, LS, and SKNBE2c). SNP data were generated using the GeneChip DNA Analysis and GeneChip chromosome copy number software (Affymetrix). SNP arrays confirmed the presence of all previously reported cytogenetic abnormalities in the cell lines, including chromosome 1p deletion, MYCN amplification, gain of 17q and 11q, and 14q deletions. In addition, the SNP arrays revealed several chromosome gains and losses not detected by CGH or karyotyping; these included gain of 8q21.1 approximately 24.3 and gain of chromosome 12 in IMR-32 cells; loss at 4p15.3 approximately 16.1 and loss at 16p12.3 approximately 13.2, 11q loss with loss of heterozygosity (LOH) at 11q14.3 approximately 23.3 in SJNB-1 cells; and loss at 8p21.2 approximately 23.3 and 9p21.3 approximately 22.1 with corresponding LOH in SHEP cells. The SNP arrays refined the mapping of the 2p amplicons in LS, BE2c, and IMR-32 cell lines, the 12q amplicon in LS cells, and also identified an 11q13 amplicon in LS cells. There was good concordance among SNP arrays, CGH, and karyotyping. SNP array analysis is a powerful tool for the detection of allelic imbalance in neuroblastoma and also allows identification of LOH without changes in copy number (uniparental disomy).
Carr
Jane
J
Northern Institute for Cancer Research, Paul O'Gorman Building, Framlington Place, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK.
Bown
Nick P
NP
Case
Marian C
MC
Hall
Andrew G
AG
Lunec
John
J
Tweddle
Deborah A
DA
D022981:Allelic Imbalance / Q000235:genetics*; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D018628:Gene Dosage / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide