Jung et al. BMC Cancer 2012, 12:382 http://www.biomedcentral.com/1471-2407/12/382 Table 3 Common high-copy number changes (>10%) Changes Chr Position (Mb) Cytoband Size (Mb) Frequency DGVa Korean CNVb AMP9 AMP64 AMP67 AMP113 AMP119 1 8 8 16 17 150.82-150.93 120.51-135-87 144.37-145.55 28.40-28.42 32.42-35.87 1q21.3 8q24.22 8q24.3 16p11.2 17q12 0.11 15.37 1.18 0.02 3.45 9 (19%) 9 (19%) 5 (10%) 6 (13%) 14 (29%) Y Y Y Y Y Y Y Y N N Page 7 of 11 Putative cancer-related genes LCE3C, LCE3B, LCE3A, LCE2D, LCE2C, LCE2B DDEF1, ENPP2, FAM83A, FAM84B, HAS2, MTSS1, MYC, NDRG1, RNF139, TG, WISP1 SCRIB, PLEC1, HSF1 CLN3 AATF, ACACA, CDC6, CSF3, ERBB2, FBXO47, GRB7, IGFBP4, LASP1, PCGF2, PERLD1, PLXDC1, PNMT, PPP1R1B, RARA, RPL19, RPL23, TBC1D3, THRA, TOP2A a Overlapping status with DGV (http://projects.tcag.ca/variation/) entries; b Overlapping status with CNVs identified from Koreans [35]. Y: overlap, N: no overlap, AMP: amplification, Chr: chromosome. groups were significantly different, with the probability of surviving decreasing with greater RAR positivity (P = 0.0052; P for trend = 0.0020) (Figure 5E). Multivariate analysis with the two significant RARs identified on univariate analysis and the covariates (age at diagnosis, stage, ER status, PR status, and HER2 sta- tus) revealed that the copy number gain status of ERBB2 (RAR-G13) was an independent indicator of poor prognosis in EBC (Hazard ratio [HR] = 5.36 , 95% CI 1.80-15.98, P = 0.003) (Table 4). When the multivariate analysis was performed with NUPR1-ERBB2 combined status and the same covariates, positivity for both RAR- Gs was found to be a strong independent indicator of poor prognosis, showing additive effects (HR = 7.31, 95% CI 2.65-20.15, P = 0.0001) (Table 4). Discussion In this study, we analyzed the genome-wide copy num- ber alteration profiles in 48 EBCs using 30K oligoarray- CGH. We delineated RARs under the assumption that commonly altered chromosomal segments in EBCs may contain driver genes essential for initiation or early pro- gression of breast tumorigenesis. It is also possible that some RARs have prognostic implications in EBC. To Figure 3 Examples of high-level copy number alterations. (A) Amplification on 8q24.22, where the MYC gene is located (red arrow). (B) Amplification on 17q12, where the ERBB2 gene is located (red arrow). (C) Homozygous deletion on 9p21, where CDKN2A and B are located (red arrow). The red and green spots in the plots on the right represent intensity ratios above 1.5 and below −1.5 on the log2 scale, respectively. The X-axis represents individual chromosomes and the Y-axis represents signal intensity ratios (tumor/normal) on the log2 scale.