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Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes

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Abstract

Understanding how cancer genes are mutated in individual tumors is an important issue with potential clinical and therapeutic impact. This is especially relevant with recently developed targeted therapies since mutated genes can be targets and/or predictors. However, to date, gene mutation profiling in individual tumors is still underexplored. Breast cancer is composed of various subtypes. We presumed that this heterogeneity reflected the involvement of different molecular mechanisms including gene mutations that affect defined signaling pathways. Unlike the majority of published mutational studies, this study was aimed to draw a mutation profile in individual tumors by screening a panel of cancer genes in the same tumor. Thus, five genes frequently mutated in breast cancers: TP53, PIK3CA, PTEN, CDH1, and AKT1 were screened in each of 120 human primary breast tumors. Mutations in at least one of these genes were found in 62.5% of the tumors, of which the majority carried a single-gene mutation. Interestingly, a substantial proportion of tumors carried mutations either in TP53 or in genes of the PI3K pathway (PIK3CA or PTEN or AKT1). These two distinct mutation patterns were significantly associated to hormone receptor expression but independent of HER2 status.

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Acknowledgments

This study was supported partially by funds from the Ligue Départementale de l’Ain and from Institut National du Cancer. We thank Pr Jean Yves Blay for helpful discussion, Thérèse Gargi for clinical data collection and documentation and George Hinkal for assistance in manuscript writing.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Laboratoire de Recherche Translationnelle, Centre Léon Bérard, 28 rue Laënnec, 69373, Lyon Cedex 08, France

    Sandrine Boyault, Claudine Navarro & Qing Wang

  2. Département de Santé Publique, Centre Léon Bérard, Lyon, France

    Youenn Drouet & Christine Lasset

  3. Département de Médecine, Centre Léon Bérard, Lyon, France

    Thomas Bachelot

  4. Département Anatomie et Cytologie Pathologique, Centre Léon Bérard, Lyon, France

    Isabelle Treilleux

  5. Centre de Ressources Biologiques, Centre Léon Bérard, Lyon, France

    Eric Tabone

  6. Centre Léon Bérard, Lyon, France

    Alain Puisieux

  7. Inserm, U590, Lyon, France

    Alain Puisieux

  8. Université de Lyon, ISPB, Lyon1, France

    Alain Puisieux

  9. Biométrie et Biologie évolutive, Université de Lyon, UMR CNRS 5558, Lyon 1, France

    Youenn Drouet & Christine Lasset

Authors
  1. Sandrine Boyault
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  2. Youenn Drouet
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  3. Claudine Navarro
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  8. Alain Puisieux
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  9. Qing Wang
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Correspondence to Qing Wang.

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Boyault, S., Drouet, Y., Navarro, C. et al. Mutational characterization of individual breast tumors: TP53 and PI3K pathway genes are frequently and distinctively mutated in different subtypes. Breast Cancer Res Treat 132, 29–39 (2012). https://doi.org/10.1007/s10549-011-1518-y

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  • DOI: https://doi.org/10.1007/s10549-011-1518-y

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