Comprehensive genetic and functional characterization of IPH‐926: a novel CDH1‐null tumour cell line from human lobular breast cancer |
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Authors: | Matthias Christgen,Henriette Bruchhardt,Catarina Hadamitzky,Cornelia Rudolph,Doris Steinemann,Dorothea Gadzicki,Britta Hasemeier,Daniel R mermann,Tim Focken,Till Krech,Matthias Ballmaier,Brigitte Schlegelberger,Hans Kreipe,Ulrich Lehmann |
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Affiliation: | 1. Institute of Pathology, Hannover Medical School, 30625 Hannover, Germany;2. Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany;3. Institute of Cell and Molecular Pathology, Hannover Medical School, 30625 Hannover, Germany;4. Department of Pediatric Hematology, Hannover Medical School, 30625 Hannover, Germany |
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Abstract: | Infiltrating lobular breast cancer (ILBC) is a clinically and biologically distinct tumour entity defined by a characteristic linear cord invasion pattern and inactivation of the CDH1 tumour suppressor gene encoding for E‐cadherin. ILBCs also lack β‐catenin expression and show aberrant cytoplasmic localization of the E‐cadherin binding protein p120‐catenin. The lack of a well‐characterized ILBC cell line has hampered the functional characterization of ILBC cells in vitro. We report the establishment of a permanent ILBC cell line, named IPH‐926, which was derived from a patient with metastatic ILBC. The DNA fingerprint of IPH‐926 verified genetic identity with the patient and had no match among the human cell line collections of several international biological resource banks. IPH‐926 expressed various epithelial cell markers but lacked expression of E‐cadherin due to a previously unreported, homozygous CDH1 241ins4 frameshift mutation. Detection of the same CDH1 241ins4 mutation in archival tumour tissue of the corresponding primary ILBC proved the clonal origin of IPH‐926 from this particular tumour. IPH‐926 also lacked β‐catenin expression and showed aberrant cytoplasmic localization of p120‐catenin. Array‐CGH analysis of IPH‐926 revealed a profile of genomic imbalances that included many distinct alterations previously observed in primary ILBCs. Spectral karyotyping of IPH‐926 showed a hyperdiploid chromosome complement and numerous clonal, structural aberrations. IPH‐926 cells were anti‐cancer drug‐resistant, clonogenic in soft agar, and tumourigenic in SCID mice. In xenograft tumours, IPH‐926 cells recapitulated the linear cord invasion pattern that defines ILBCs. In summary, IPH‐926 significantly extends the biological spectrum of the established breast cancer cell lines and will facilitate functional analyses of genuine human ILBC cells in vitro and in vivo. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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Keywords: | lobular breast cancer CDH1 mutation array CGH SCID mouse xenograft model chemoresistance |
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