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Establishment and characterisation of a new breast cancer xenograft obtained from a woman carrying a germline BRCA2 mutation.

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Article
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De Plater, L. ; Lauge, A. ; Guyader, Christophe ; Poupon, M.F. ; Assayag, F. ; De Crémoux, Patricia ; Vincent-Salomon, A. ; Stoppa-Lyonnet, D. ; Siqal-Zafrani, B. ; Fontaine, J.J. ; Brough, R. ; Lord, C.J. ; Ashworth, A. ; Cottu, P. ; Decaudin, D. ; Marangoni, E.

BRITISH JOURNAL OF CANCER

1Preclinical Investigation Unit, Institut Curie – Translational Research Department, Hôpital St Louis, Quadrilatère historique, Porte 13, 1, Ave Claude Vellefaux, Paris 75010, France.2 Department of Tumor Biology, Institut Curie, Paris, France 3INSERM U830, Institut Curie, Paris, France 4University Paris Descartes, Paris, France 5National Veterinary School of Maisons Alfort, Maisons-Alfort, France 6Gene Function Laboratory, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, UK 7Department of Medical Oncology, Institut Curie, Paris, France

2010

Article

Abstract BACKGROUND: The BRCA2 gene is responsible for a high number of hereditary breast and ovarian cancers, and studies of the BRCA2 biological functions are limited by the lack of models that resemble the patient's tumour features. The aim of this study was to establish and characterise a new human breast carcinoma xenograft obtained from a woman carrying a germline BRCA2 mutation. METHODS: A transplantable xenograft was obtained by grafting a breast cancer sample into nude mice. The biological and genetic profiles of the xenograft were compared with that of the patient's tumour using histology, immunohistochemistry (IHC), BRCA2 sequencing, comparative genomic hybridisation (CGH), and qRT-PCR. Tumour response to standard chemotherapies was evaluated. RESULTS: Histological profile identified the tumour as a basal-like triple-negative breast cancer. Targeted BRCA2 DNA sequencing of the xenograft showed the presence of the mutation previously identified in the carrier. Comparative genomic hybridisation array profiles of the primary tumour and the xenograft revealed a high number of similar genetic alterations. The therapeutic assessment of the xenograft showed sensitivity to anthracyclin-based chemotherapy and resistance to docetaxel. The xenograft was also highly sensitive to radiotherapy and cisplatin-based treatments. CONCLUSIONS: This study describes a new human breast cancer xenograft obtained from a BRCA2-mutated patient. This xenograft provides a new model for the pre-clinical drug development and for the exploration of the drug response biological basis.
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