Establishment and characterisation of a new breast cancer xenograft obtained from a woman carrying a germline BRCA2 mutation.
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.
de Plater
L
L
Preclinical Investigation Unit, Institut Curie - Translational Research Department, Hôpital St Louis, Quadrilatère historique, Porte 13, 1, Ave Claude Vellefaux, Paris 75010, France.
Laugé
A
A
Guyader
C
C
Poupon
M-F
MF
Assayag
F
F
de Cremoux
P
P
Vincent-Salomon
A
A
Stoppa-Lyonnet
D
D
Sigal-Zafrani
B
B
Fontaine
J-J
JJ
Brough
R
R
Lord
C J
CJ
Ashworth
A
A
Cottu
P
P
Decaudin
D
D
Marangoni
E
E
D000328:Adult; D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D024522:Genes, BRCA2; D018095:Germ-Line Mutation / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D018943:Anthracyclines