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Open Access 01-12-2012 | Research article

Simultaneous copy number gains of NUPR1 and ERBB2 predicting poor prognosis in early-stage breast cancer

Authors: Seung-Hyun Jung, Ahwon Lee, Seon-Hee Yim, Hae-Jin Hu, Chungyoul Choe, Yeun-Jun Chung

Published in: BMC Cancer | Issue 1/2012

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/382/prepub

Title: Simultaneous copy number gains of NUPR1 and ERBB2 predicting poor prognosis in early-stage breast cancer
Authors: Seung-Hyun Jung
Ahwon Lee
Seon-Hee Yim
Hae-Jin Hu
Chungyoul Choe
Yeun-Jun Chung
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-12-382

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