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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 1/2012

Open Access 01-08-2012 | Preclinical Study

Oncogene amplification in male breast cancer: analysis by multiplex ligation-dependent probe amplification

Authors: Robert Kornegoor, Cathy B. Moelans, Anoek H. J. Verschuur-Maes, Marieke C. H. Hogenes, Peter C. de Bruin, Joost J. Oudejans, Luigi Marchionni, Paul J. van Diest

Published in: Breast Cancer Research and Treatment | Issue 1/2012

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Abstract

Gene amplification is an important mechanism for oncogene activation, a crucial step in carcinogenesis. Compared to female breast cancer, little is known on the genetic makeup of male breast cancer, because large series are lacking. Copy number changes of 21 breast cancer related genes were studied in 110 male breast cancers using multiplex ligation-dependent probe amplification. A ratio of >1.3 was regarded indicative for gene copy number gain and a ratio >2.0 for gene amplification. Data were correlated with clinicopathological features, prognosis and 17 genes were compared with a group of female breast cancers. Gene copy number gain of CCND1, TRAF4, CDC6 and MTDH was seen in >40 % of the male breast cancer cases, with also frequent amplification. The number of genes with copy number gain and several single genes were associated with high grade, but only CCND1 amplification was an independent predictor of adverse survival in Cox regression (p = 0.015; hazard ratio 3.0). In unsupervised hierarchical clustering a distinctive group of male breast cancer with poor prognosis (p = 0.009; hazard ratio 3.4) was identified, characterized by frequent CCND1, MTDH, CDC6, ADAM9, TRAF4 and MYC copy number gain. Compared to female breast cancers, EGFR (p = 0.005) and CCND1 (p = 0.041) copy number gain was more often seen in male breast cancer, while copy number gain of EMSY (p = 0.004) and CPD (p = 0.001) and amplification in general was less frequent. In conclusion, several female breast cancer genes also seem to be important in male breast carcinogenesis. However, there are also clear differences in copy number changes between male and female breast cancers, pointing toward differences in carcinogenesis between male and female breast cancer and emphasizing the importance of identifying biomarkers and therapeutic agents based on research in male breast cancer. In addition CCND1 amplification seems to be an independent prognosticator in male breast cancer.
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Metadata
Title
Oncogene amplification in male breast cancer: analysis by multiplex ligation-dependent probe amplification
Authors
Robert Kornegoor
Cathy B. Moelans
Anoek H. J. Verschuur-Maes
Marieke C. H. Hogenes
Peter C. de Bruin
Joost J. Oudejans
Luigi Marchionni
Paul J. van Diest
Publication date
01-08-2012
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-012-2051-3

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