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

• Published in: British journal of cancer Vol. 103; no. 8; pp. 1192 - 1200
• Main Authors: de Plater, L, Laugé, A, Guyader, C, Poupon, M-F, Assayag, F, de Cremoux, P, Vincent-Salomon, A, Stoppa-Lyonnet, D, Sigal-Zafrani, B, Fontaine, J-J, Brough, R, Lord, C J, Ashworth, A, Cottu, P, Decaudin, D, Marangoni, E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.10.2010; Nature Publishing Group
• Subjects: 631/208/737; 631/67/1059/153; 692/308/2778; 692/699/67/1347; Adult; Animals; Anthracyclines - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer Research; Cancer therapies; Carcinoma, Ductal, Breast - drug therapy; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - pathology; Cell Culture Techniques; Cell Line, Tumor; Comparative Genomic Hybridization; DNA Mutational Analysis; DNA repair; Drug Resistance; Epidemiology; Female; Genes, BRCA2; Genetic testing; Germ-Line Mutation - physiology; Heterozygote; Humans; Medical research; Mice; Mice, Nude; Molecular Medicine; Mutation; Neoplasm Transplantation; Oncology; Ovarian cancer; Translational Therapeutics; Transplantation, Heterologous; Tumors; Womens health; Xenograft Model Antitumor Assays - methods; France; Paris France; BRCA2 mutation; human breast cancer xenograft; preclinical model
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605900

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.