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Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines

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Abstract

Breast cancer has for long been recognized as a highly diverse tumor group, but the underlying genetic basis has been elusive. Here, we report an extensive molecular characterization of a collection of 41 human breast cancer cell lines. Protein and gene expression analyses indicated that the collection of breast cancer cell lines has retained most, if not all, molecular characteristics that are typical for clinical breast cancers. Gene mutation analyses identified 146 oncogenic mutations among 27 well-known cancer genes, amounting to an average of 3.6 mutations per cell line. Mutations in genes from the p53, RB and PI3K tumor suppressor pathways were widespread among all breast cancer cell lines. Most important, we have identified two gene mutation profiles that are specifically associated with luminal-type and basal-type breast cancer cell lines. The luminal mutation profile involved E-cadherin and MAP2K4 gene mutations and amplifications of Cyclin D1, ERBB2 and HDM2, whereas the basal mutation profile involved BRCA1, RB1, RAS and BRAF gene mutations and deletions of p16 and p14ARF. These subtype-specific gene mutation profiles constitute a genetic basis for the heterogeneity observed among human breast cancers, providing clues for their underlying biology and providing guidance for targeted pharmacogenetic intervention in breast cancer patients.

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Acknowledgments

We received grant support from Susan G. Komen Breast Cancer Foundation, Erasmus MC Mrace, Dutch Cancer Society, Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO), Association for International Cancer Research and Survivorsland Foundation, Vlissingen, The Netherlands. We appreciate the technical assistance of Michel Molier, Sofia Zuňiga, Mieke Timmermans, Jurjen J. Boonstra, Hein Sleddens and members of the Pathology Immunohistochemistry laboratories at Erasmus MC. We thank Dr. Jörg Volkland, Dr. Nelleke Gruis, Dr. Goos van Muijen and Dr. Jan Verheijen for kindly providing us with M14 cells.

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Authors and Affiliations

  1. Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Antoinette Hollestelle, Jord H. A. Nagel, Marcel Smid, Fons Elstrodt, Marijke Wasielewski, Marieke J. Rozendaal, Muhammad Riaz, Daphne G. Koopman, Jan G. M. Klijn, John A. Foekens, John W. M. Martens & Mieke Schutte

  2. Cancer Genomics Centre, Rotterdam, The Netherlands

    Marcel Smid, Marijke Wasielewski & John A. Foekens

  3. Department of Neurology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, The Netherlands

    Pim J. French & Bertie H. C. G. M. de Leeuw

  4. Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, The Netherlands

    Ellen C. Zwarthoff, Winand N. M. Dinjens & Michael A. den Bakker

  5. Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands

    Justine K. Peeters & Peter J. van der Spek

  6. Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Daniel den Hoed Cancer Center, Erasmus University Medical Center, Rotterdam, The Netherlands

    Timo L. M. ten Hagen

  7. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands

    Suzanne Lam, Amina Teunisse & Aart G. Jochemsen

  8. Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands

    Ser Sue Ng & Hans Clevers

  9. Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Stephen P. Ethier

Authors
  1. Antoinette Hollestelle
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  2. Jord H. A. Nagel
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  3. Marcel Smid
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  4. Suzanne Lam
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  6. Marijke Wasielewski
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  7. Ser Sue Ng
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  10. Marieke J. Rozendaal
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  11. Muhammad Riaz
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  12. Daphne G. Koopman
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  13. Timo L. M. ten Hagen
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  14. Bertie H. C. G. M. de Leeuw
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  17. Peter J. van der Spek
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  18. Jan G. M. Klijn
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  22. Aart G. Jochemsen
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  23. Michael A. den Bakker
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  24. John A. Foekens
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  25. John W. M. Martens
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  26. Mieke Schutte
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Correspondence to Antoinette Hollestelle or Mieke Schutte.

Additional information

Antoinette Hollestelle and Jord H. A. Nagel contributed equally to this work.

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Hollestelle, A., Nagel, J.H.A., Smid, M. et al. Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast Cancer Res Treat 121, 53–64 (2010). https://doi.org/10.1007/s10549-009-0460-8

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