**3.2 Measurement of neuroblastoma DNA copy number aberrations (CNAs)**

BAC technique has increasing been applied in detecting structural changes in chromosomes, such as copy number aberrations (CANs) and rearrangement. Mosse et al (Mosse, Greshock et al. 2005) generated 4135 BAC clones spanning the human genome at about 1.0 Mb resolution as targets for array-based comparative genomic hybridization (aCGH) experiments (Greshock, Naylor et al. 2004). They measured the relevance of neuroblastoma DNA copy number changes (CNAs) in forty-two human neuroblastoma cell lines. They found that all cell lines exhibited CNAs ranging from 2% to 41% of the genome. Chromosome 17 showed the highest frequency of CANs. The most frequent region of gain with high-level amplification localized to 2p24.22-2p24.3 detected in 81% of cell lines (Mosse, Greshock et al. 2005). Potential oncogenes such as MYCN, NAG and DDX1 were located in these regions. The less frequent region of gain localized to 17q23.2, 17q23.3-17q24.1, 17q24.1-17q24.2, 17q25.2-17q25.3 was detected in about 70% of the cell lines. Potential oncogene BIRC5 was localized in these regions. Although gain of 17q material was common, this low level gain of chromosomal material was rather complicated (Mosse, Greshock et al. 2005). The most frequent hemizygous deletion localized to a 4.0 Mb region at 1p36.23-36.32, was detected in 60% of the cell lines. Potential tumor suppressor genes TP73, CHD5, RPL22 and HKR3 were also localized. A 10.4 Mb region at 11q23.3-11q25 was detected in 36% of the cell lines, and the potential tumor suppressor gene CHEK1 was found there as well (Mosse, Greshock et al. 2005). Overall, the array CGH could be reliable in examining DNA copy number aberrations including single copy gain or loss. Compared to the data with standard techniques, data from array CGH correlates well with known aberrations detected by standard techniques. Therefore, array CGH can be applied to identify novel regions of genomic imbalance.
