Jung et al. BMC Cancer 2012, 12:382 http://www.biomedcentral.com/1471-2407/12/382 R E S E A R C H A R T I C L E Open Access Simultaneous copy number gains of NUPR1 and ERBB2 predicting poor prognosis in early-stage breast cancer Seung-Hyun Jung1,2, Ahwon Lee3, Seon-Hee Yim1,4, Hae-Jin Hu1,2, Chungyoul Choe1,2 and Yeun-Jun Chung1,2* Abstract Background: The full extent of chromosomal alterations and their biological implications in early breast carcinogenesis has not been well examined. In this study, we aimed to identify chromosomal alterations associated with poor prognosis in early-stage breast cancers (EBC). Methods: A total of 145 EBCs (stage I and II) were examined in this study. We analyzed copy number alterations in a discovery set of 48 EBCs using oligoarray-comparative genomic hybridization. In addition, the recurrently altered regions (RARs) associated with poor prognosis were validated using an independent set of 97 EBCs. Results: A total of 23 RARs were defined in the discovery set. Six were commonly detected in both stage I and II groups (> 50%), suggesting their connection with early breast tumorigenesis. There were gains on 1q21.2-q21.3, 8q24.13, 8q24.13-21, 8q24.3, and 8q24.3 and a loss on 8p23.1-p22. Among the 23 RARs, copy number gains on 16p11.2 (NUPR1) and 17q12 (ERBB2) showed a significant association with poor survival (P = 0.0186 and P = 0.0186, respectively). The patients simultaneously positive for both gains had a significantly worse prognosis (P = 0.0001). In the independent replication, the patients who were double-positive for NUPR1-ERBB2 gains also had a significantly poorer prognosis on multivariate analysis (HR = 7.31, 95% CI 2.65-20.15, P = 0.0001). Conclusions: The simultaneous gain of NUPR1 and ERBB2 can be a significant predictor of poor prognosis in EBC. Our study will help to elucidate the molecular mechanisms underlying early-stage breast cancer tumorigenesis. This study also highlights the potential for using combinations of copy number alterations as prognosis predictors for EBC. Background Breast cancer is the most common female cancer and the leading cause of cancer-related mortality in women worldwide [1,2]. Due to mammographic screening and advances in chemotherapy, breast cancer mortality rates have decreased in developed countries since 1990 [3,4]. Nonetheless, axillary-node negative patients treated by surgery showed a ten-year recurrence rate of approxi- mately 20% [5]. The five-year survival rate of stage I and II breast cancer patients is reported to be approximately 80% to 88% [6-8]. This means that 10-20% of early-stage * Correspondence: yejun@catholic.ac.kr 1Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Republic of Korea 2Department of Microbiology, The Catholic University of Korea, Seoul, South Korea Full list of author information is available at the end of the article breast cancer (EBC) patients have poor clinical out- comes. When considering the large impact that breast cancer has on public health, it is worth investigating genetic mechanisms underlying poor clinical outcomes of some EBCs. Genomic instability is one of the hallmarks of breast cancer. DNA copy number aberrations, commonly detected phenomena in cancer lesions, are thought to be involved in tumorigenesis and to affect cancer pheno- types [9]. Different patterns of copy number alterations are associated with distinct gene expression patterns and clinical characteristics of breast cancer [10]. A number of chromosomal alterations and subsequent expression changes have been investigated to determine their impli- cations in clinical phenotypes or prognosis. These inves- tigations have resulted in the identification of some cancer-related genes in breast cancer [11]. For example, © 2012 Jung et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.