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

Hollestelle, A. and Nagel, J. H. and Smid, M. and Lam, S. and Elstrodt, F. and Wasielewski, M. and Ng, S.S. and French, P. J. and Peeters, J. K. and Rozendaal, M. J. and Riaz, M. and Koopman, D. G. and Hagen Ten, T. L. and Leeuw de, B. H. and Zwarthoff, E. C. and Teunisse, A. and Spek van der, P. J. and Klijn, J. G. and Dinjens, W. N. and Ethier, S. P. and Clevers, H. and Jochemsen, A. G. and Bakker den, M. A. and Foekens, J. A. and Martens, J. W. and Schutte, M. (2009) Distinct gene mutation profiles among luminal-type and basal-type breast cancer cell lines. Breast cancer research and treatment. ISSN 1573-7217.

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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.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:7008
Deposited On:25 Jan 2010 01:00
Last Modified:13 Oct 2010 12:51

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