Abstract P6-06-02: Molecular characterization of a patient-derived xenograft (PDX) resource for triple negative breast cancer

Abstract

Abstract The Jackson Laboratory (JAX) has developed a resource of human tumors implanted into immune deficient mice (patient derived xenografts; PDX) as a platform for testing standard of care and novel therapeutic options for Triple Negative Breast Cancer. PDX models provide an advantage over cell culture based models for testing therapeutic interventions because they retain properties such as tumor cell heterogeneity that are critical to the biological properties of a patient’s tumor and response to treatment. Tumor material acquired from biopsy or surgical resection was implanted subcutaneously into the flank of immune deficient NOD-scid IL2r gamma-chain null (NSG) mice. The PDX resource currently contains 21 established breast cancer PDX models (12 TNBC) with 24 additional models currently in development. Two of the established TNBC PDX models have BRCA1 mutations. The median age of the patients from whom tumor material was obtained for all breast models is 53 (45-89). Tumors that successfully engrafted were characterized for somatic mutations using the new JAX Clinical Cancer Panel, Copy Number Variants using the Affymetrix human 6.0 SNP array, and gene expression using both Affymetrix U133 plus v2 and RNA-Seq. Normalized gene expression was analyzed for characteristic patterns in a pan-cancer approach across all PDX models and further compared with the previously identified TNBC molecular subtypes (Lehmann et al. 2011. JCI 121:2750-2767). The combination of principal components analysis and classification via expression pattern resulted in putative matches of models to most of the known molecularly defined subtypes of TNBC tumors. Tumor bearing mice for the TNBC PDX models have been treated with docetaxel, cisplatin, cyclophosphamide and doxorubicin. Preliminary studies of tumor response to these treatment regimes revealed systematic differences that can be correlated with features of the genomic analysis, including expression subtype characterization. The JAX collection of TNBC cancer PDX models is a well-annotated, publically available resource of models with deep genomic characterization and standard of care therapy response data for use in the development of advanced therapeutic options. Genomically defined subgroups within the collection suggest strategies to refine patient selection and treatment algorithms. Information about the models along with summarized genomic data is publicly available at the Mouse Tumor Biology database PDX web portal (http://tumor.informatics.jax.org). Citation Format: Joel H Graber, James G Keck, Susan D Airhart, Carol J Bult, Edison T Liu. Molecular characterization of a patient-derived xenograft (PDX) resource for triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-06-02.