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Breast Cancer Research
Published in: Breast Cancer Research 2/2012

Open Access 01-04-2012 | Research article

Relevance of PTEN loss in brain metastasis formation in breast cancer patients

Authors: Harriet Wikman, Katrin Lamszus, Niclas Detels, Liubov Uslar, Michaela Wrage, Christian Benner, Ina Hohensee, Bauke Ylstra, Kathrin Eylmann, Marc Zapatka, Guido Sauter, Dirk Kemming, Markus Glatzel, Volkmar Müller, Manfred Westphal, Klaus Pantel

Published in: Breast Cancer Research | Issue 2/2012

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Abstract

Introduction

With the improvement of therapeutic options for the treatment of breast cancer, the development of brain metastases has become a major limitation to life expectancy in many patients. Therefore, our aim was to identify molecular markers associated with the development of brain metastases in breast cancer.

Methods

Patterns of chromosomal aberrations in primary breast tumors and brain metastases were compared with array-comparative genetic hybridization (CGH). The most significant region was further characterized in more detail by microsatellite and gene-expression analysis, and finally, the possible target gene was screened for mutations.

Results

The array CGH results showed that brain metastases, in general, display similar chromosomal aberrations as do primary tumors, but with a notably higher frequency. Statistically significant differences were found at nine different chromosomal loci, with a gain and amplification of EGFR (7p11.2) and a loss of 10q22.3-qter being among the most significant aberrations in brain metastases (P < 0.01; false discovery rate (fdr) < 0.04). Allelic imbalance (AI) patterns at 10q were further verified in 77 unmatched primary tumors and 21 brain metastases. AI at PTEN loci was found significantly more often in brain metastases (52%) and primary tumors with a brain relapse (59%) compared with primary tumors from patients without relapse (18%; P = 0.003) or relapse other than brain tumors (12%; P = 0.006). Loss of PTEN was especially frequent in HER2-negative brain metastases (64%). Furthermore, PTEN mRNA expression was significantly downregulated in brain metastases compared with primary tumors, and PTEN mutations were frequently found in brain metastases.

Conclusions

These results demonstrate that brain metastases often show very complex genomic-aberration patterns, suggesting a potential role of PTEN and EGFR in brain metastasis formation.
Appendix
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Metadata
Title
Relevance of PTEN loss in brain metastasis formation in breast cancer patients
Authors
Harriet Wikman
Katrin Lamszus
Niclas Detels
Liubov Uslar
Michaela Wrage
Christian Benner
Ina Hohensee
Bauke Ylstra
Kathrin Eylmann
Marc Zapatka
Guido Sauter
Dirk Kemming
Markus Glatzel
Volkmar Müller
Manfred Westphal
Klaus Pantel
Publication date
01-04-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 2/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3150

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