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01-08-2009 | Preclinical Study

Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH

Authors: Simon A. Joosse, Erik H. van Beers, Ivon H. G. Tielen, Hugo Horlings, Johannes L. Peterse, Nicoline Hoogerbrugge, Marjolijn J. Ligtenberg, Lodewyk F. A. Wessels, Priscilla Axwijk, Senno Verhoef, Frans B. L. Hogervorst, Petra M. Nederlof

Published in: Breast Cancer Research and Treatment | Issue 3/2009

Abstract

Background While new defects in BRCA1 are still being found, it is unclear whether current breast cancer diagnostics misses many BRCA1-associated cases. A reliable test that is able to indicate the involvement of BRCA1 deficiency in cancer genesis could support decision making in genetic counselling and clinical management. To find BRCA1-specific markers and explore the effectiveness of the current diagnostic strategy, we designed a classification method, validated it and examined whether we could find BRCA1-like breast tumours in a group of patients initially diagnosed as non-BRCA1/2 mutation carriers. Methods A classifier was built based on array-CGH profiles of 18 BRCA1-related and 32 control breast tumours, and validated on independent sets of 16 BRCA1-related and 16 control breast carcinomas. Subsequently, we applied the classifier to 48 breast tumours of patients from Hereditary Breast and Ovarian Cancer (HBOC) families in whom no germ line BRCA1/BRCA2 mutations were identified. Results The classifier showed an accuracy of 91% when applied to the validation sets. In 48 non-BRCA1/2 patients, only two breast tumours presented a BRCA1-like CGH profile. Additional evidence for BRCA1 dysfunction was found in one of these tumours. Conclusion We here describe the specific chromosomal aberrations in BRCA1-related breast carcinomas. We developed a predictive genetic test for BRCA1-association and show that BRCA1-related tumours can still be identified in HBOC families after routine DNA diagnostics.

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Title: Prediction of BRCA1-association in hereditary non-BRCA1/2 breast carcinomas with array-CGH
Authors: Simon A. Joosse
Erik H. van Beers
Ivon H. G. Tielen
Hugo Horlings
Johannes L. Peterse
Nicoline Hoogerbrugge
Marjolijn J. Ligtenberg
Lodewyk F. A. Wessels
Priscilla Axwijk
Senno Verhoef
Frans B. L. Hogervorst
Petra M. Nederlof
Publication date: 01-08-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-0117-z

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