A Patient-Derived Xenograft Preclinical Model for Triple Negative Breast Cancer to Evaluate PDJ Amplicon Heterogeneity and Chemotherapeutic Induction

We applied DNA content flow cytometry to ten patient derived triple negative breast cancer (TNBC) xenografts (PDXs) from the Baylor College of Medicine (BCM). We interrogated purified sorted tumor fractions from each sample with whole genome copy number variant (CNV) analyses. These identified a variety of somatic genomic lesions that are common in TNBC including three cases with 9p24.1 amplification targeting PD-L1-PDL2 and JAK2 (PDJ amplicon) and recurring focal amplicons of oncogenic drivers found commonly in the TNBC PDXs including MYC and EGFR. In addition, homozygous deletions of known tumor suppressor genes including PTEN, CDKN2A, RB1, and BRCA2, and unique targets such as CUX1 and FYN were identified. Of the three PDJ-positive amplified PDXs, 2/3 two had focal MYC amplifications and 1/3 had a RB1 homozygous deletion. We applied DNA content based flow sorting to isolate the nuclei of human tumor populations from breast cancer patient derived xenograft (PDX) models. We coupled this strategy with oligonucleotide array CGH (aCGH) thereby obtaining high definition genomic profiles of clonal populations from each tumor. These included two pairs of pre and post neoadjuvant therapy treated TNBC cases.