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Platform comparisons for identification of breast cancers with a BRCA-like copy number profile

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Previously, we employed bacterial artificial chromosome (BAC) array comparative genomic hybridization (aCGH) profiles from BRCA1 and -2 mutation carriers and sporadic tumours to construct classifiers that identify tumour samples most likely to harbour BRCA1 and -2 mutations, designated ‘BRCA1 and -2-like’ tumours, respectively. The classifiers are used in clinical genetics to evaluate unclassified variants, and patients for which no good quality germline DNA is available. Furthermore, we have shown that breast cancer patients with BRCA-like tumour aCGH profiles benefit substantially from platinum-based chemotherapy, potentially due to their inability to repair DNA double strand breaks (DSB), providing a further important clinical application for the classifiers. The BAC array technology has been replaced with oligonucleotide arrays. To continue clinical use of existing classifiers, we mapped oligonucleotide aCGH data to the BAC domain, such that the oligonucleotide profiles can be employed as in the BAC classifier. We demonstrate that segmented profiles derived from oligonucleotide aCGH show high correlation with BAC aCGH profiles. Furthermore, we trained a support vector machine score to objectify aCGH profile quality. Using the mapped oligonucleotide aCGH data, we show equivalence in classification of biologically relevant cases between BAC and oligonucleotide data. Furthermore, the predicted benefit of DSB inducing chemotherapy due to a homologous recombination defect is retained. We conclude that oligonucleotide aCGH data can be mapped to and used in the previously developed and validated BAC aCGH classifiers. Our findings suggest that it is possible to map copy number data from any other technology in a similar way.

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Abbreviations

aCGH:

Array comparative genomic hybridization

BAC:

Bacterial artificial chromosome

SVM:

Support vector machine

HR:

Homologous recombination

DSB:

Double strand break

ER:

Oestrogen receptor

FEC:

5-Fluorouracil, epirubicin, cyclophosphamide

CTC:

Carboplatin, thiotepa, cyclophosphamide

HER2:

Human epidermal growth factor receptor 2

PR:

Progesterone receptor

PARP1:

Poly(ADP)ribose polymerase-1

DNA:

Deoxyribonucleic acid

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Acknowledgments

The authors thank Marieke Vollebergh for discussion and Tesa Severson for critically reading the article. This study was carried out within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), project Breast CARE grant 030-104, and Life Sciences Center Amsterdam (LSCA) Validation fund.

Conflict of interest

SC Linn and PM Nederlof are named inventors on a patent application for the BRCA1 and -2-like array comparative genomics hybridization classifiers. The other authors do not disclose any conflict of interest.

Author information

Authors and Affiliations

  1. Division of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, The Netherlands

    Philip C. Schouten, Linde M. Braaf, Lennart Mulder, Esther H. Lips, Jelle Wesseling, Sabine C. Linn & Petra M. Nederlof

  2. Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Ewald van Dyk, Jorma J. de Ronde & Lodewyk F. A. Wessels

  3. Department of Epidemiology and Biostatistics, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Michael Hauptmann

  4. Genomics Core Facility, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Laura Holtman

  5. Faculty of EEMCS, TU Delft, Delft, The Netherlands

    Lodewyk F. A. Wessels

  6. Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Sabine C. Linn

  7. Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Jelle Wesseling & Petra M. Nederlof

Authors
  1. Philip C. Schouten
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  2. Ewald van Dyk
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  3. Linde M. Braaf
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  4. Lennart Mulder
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  5. Esther H. Lips
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  8. Jelle Wesseling
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  11. Sabine C. Linn
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  12. Petra M. Nederlof
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Corresponding author

Correspondence to Petra M. Nederlof.

Additional information

Philip C. Schouten and Ewald van Dyk contributed equally to this study.

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Schouten, P.C., van Dyk, E., Braaf, L.M. et al. Platform comparisons for identification of breast cancers with a BRCA-like copy number profile. Breast Cancer Res Treat 139, 317–327 (2013). https://doi.org/10.1007/s10549-013-2558-2

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  • DOI: https://doi.org/10.1007/s10549-013-2558-2

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