Breast Cancer Research and Treatment

, Volume 121, Issue 1, pp 53–64 | Cite as

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

  • Antoinette Hollestelle
  • Jord H. A. Nagel
  • Marcel Smid
  • Suzanne Lam
  • Fons Elstrodt
  • Marijke Wasielewski
  • Ser Sue Ng
  • Pim J. French
  • Justine K. Peeters
  • Marieke J. Rozendaal
  • Muhammad Riaz
  • Daphne G. Koopman
  • Timo L. M. ten Hagen
  • Bertie H. C. G. M. de Leeuw
  • Ellen C. Zwarthoff
  • Amina Teunisse
  • Peter J. van der Spek
  • Jan G. M. Klijn
  • Winand N. M. Dinjens
  • Stephen P. Ethier
  • Hans Clevers
  • Aart G. Jochemsen
  • Michael A. den Bakker
  • John A. Foekens
  • John W. M. Martens
  • Mieke Schutte
Preclinical study

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.

Keywords

Breast cancer subtypes Histological classification Intrinsic subtypes Molecular classification Mutation analysis 

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Antoinette Hollestelle
    • 1
  • Jord H. A. Nagel
    • 1
  • Marcel Smid
    • 1
    • 2
  • Suzanne Lam
    • 7
  • Fons Elstrodt
    • 1
  • Marijke Wasielewski
    • 1
    • 2
  • Ser Sue Ng
    • 8
  • Pim J. French
    • 3
  • Justine K. Peeters
    • 5
  • Marieke J. Rozendaal
    • 1
  • Muhammad Riaz
    • 1
  • Daphne G. Koopman
    • 1
  • Timo L. M. ten Hagen
    • 6
  • Bertie H. C. G. M. de Leeuw
    • 3
  • Ellen C. Zwarthoff
    • 4
  • Amina Teunisse
    • 7
  • Peter J. van der Spek
    • 5
  • Jan G. M. Klijn
    • 1
  • Winand N. M. Dinjens
    • 4
  • Stephen P. Ethier
    • 9
  • Hans Clevers
    • 8
  • Aart G. Jochemsen
    • 7
  • Michael A. den Bakker
    • 4
  • John A. Foekens
    • 1
    • 2
  • John W. M. Martens
    • 1
  • Mieke Schutte
    • 1
  1. 1.Department of Medical Oncology, Josephine Nefkens InstituteErasmus University Medical CenterRotterdamThe Netherlands
  2. 2.Cancer Genomics CentreRotterdamThe Netherlands
  3. 3.Department of Neurology, Josephine Nefkens InstituteErasmus University Medical CenterRotterdamThe Netherlands
  4. 4.Department of Pathology, Josephine Nefkens InstituteErasmus University Medical CenterRotterdamThe Netherlands
  5. 5.Department of BioinformaticsErasmus University Medical CenterRotterdamThe Netherlands
  6. 6.Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Daniel den Hoed Cancer CenterErasmus University Medical CenterRotterdamThe Netherlands
  7. 7.Department of Molecular Cell BiologyLeiden University Medical CenterLeidenThe Netherlands
  8. 8.Hubrecht Institute for Developmental Biology and Stem Cell ResearchUtrechtThe Netherlands
  9. 9.Barbara Ann Karmanos Cancer InstituteDetroitUSA

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