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Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women

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Abstract

Basal-like and triple-negative breast cancers usually display a high level of genomic instability and often carry TP53 mutations. Mutations in EGFR have been reported in about 10 % triple-negative tumours from Chinese women, and there is some evidence that triple-negative and basal-like tumours might carry additional mutations against which targeted therapies are available. We, therefore, sought to determine the frequency of 238 targetable mutations in 19 oncogenes (including EGFR) in a panel of basal-like and triple-negative breast cancers from Caucasian women. We used the OncoCarta panel to screen for 238 mutations across 19 common oncogenes in 107 basal-like and triple-negative breast cancers from Caucasian women. Mutations were then verified using Sanger sequencing or primer extension by iPLEX. We identified and validated 10 mutations across five genes. Most of the mutations were observed in the PIK3CA gene (18/107, 16.8 %), while mutations in KRAS, NRAS, MET and AKT1 were present in only one tumour each (1/107, 0.9 %). Among the missense substitutions in PIK3CA the point mutation resulting in the amino acid change H1047R was the most frequent (8/18, 44 %). All mutations were mutually exclusive, apart from one basal-like breast tumour which harboured mutations in both MET (p.T992I) and PIK3CA (p.H1047R). We did not identify any mutations in the EGFR gene. In conclusion, we found that with the exception of mutations in PIK3CA, these actionable oncogenic mutations on the Oncocarta panel are rare in basal-like and triple-negative breast cancers from Caucasian women. Custom panels, designed to detect mutations identified by exome sequencing of basal-like and triple-negative breast cancers, are, therefore, needed to identify women who might be eligible for targeted treatment.

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Acknowledgments

This project was supported by a grant from the National Breast Cancer Foundation. In addition, PTS is funded by a fellowship from the National Breast Cancer Foundation, Australia; GCT is a Senior Principal Research Fellow of the NHMRC. ET was supported by the Max Weber-Programm des Freistaates Bayern zur Hochbegabtenförderung nach dem Bayerischen Eliteförderungsgesetz” of the State of Bavaria and a grant from the Deans’ Office of the faculty for chemistry and pharmacy of the Ludwig-Maximilians University.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Cancer Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia

    E. Tilch, T. Seidens, S. Cocciardi & G. Chenevix Trench

  2. The Royal Brisbane and Women’s Hospital, UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, QLD, 4029, Australia

    L. E. Reid, P. T. Simpson, A. C. Vargas, M. C. Cummings & S. R. Lakhani

  3. Department of Pathology and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, 3052, Australia

    D. Byrne & S. B. Fox

  4. School of Medicine, The University of Queensland, Herston, Brisbane, QLD, 4029, Australia

    M. C. Cummings, S. R. Lakhani & G. Chenevix Trench

  5. The Royal Brisbane and Women’s Hospital, Pathology Queensland, Herston, Brisbane, QLD, 4029, Australia

    M. C. Cummings & S. R. Lakhani

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  1. E. Tilch
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  2. T. Seidens
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  3. S. Cocciardi
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  4. L. E. Reid
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  5. D. Byrne
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  6. P. T. Simpson
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  7. A. C. Vargas
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  8. M. C. Cummings
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  9. S. B. Fox
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  10. S. R. Lakhani
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  11. G. Chenevix Trench
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Corresponding author

Correspondence to G. Chenevix Trench.

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E. Tilch and T. Seidens have contributed equally to this study.

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Tilch, E., Seidens, T., Cocciardi, S. et al. Mutations in EGFR, BRAF and RAS are rare in triple-negative and basal-like breast cancers from Caucasian women. Breast Cancer Res Treat 143, 385–392 (2014). https://doi.org/10.1007/s10549-013-2798-1

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  • DOI: https://doi.org/10.1007/s10549-013-2798-1

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