Center Initiated Projects (CIPs) are proposed by the McDonnell Genome Institute to help fulfill the mission and strategic vision of the NHGRI and NIH. All CIP data will be released in a timely manner via appropriate databases in accordance with NHGRI and NIH guidelines.
Project Summary: We originally pursued the sequencing of a single xenograft passage of a basal-type breast tumor as one of a quartet of matched samples from a single patient. Our primary goal in doing so was because of the widespread interest in xenotransplants in the oncology and therapy development community, and a fundamental desire to characterize with exquisite resolution, the genomic relatedness of these two tumors. Having found that the primary and xenograft genomes remain somewhat similar but the xenograft develops differences in the prevalence of certain mutations in the tumor cell population, as well as copy number changes, and given that similar trends were observed in the metastatic disease, we are compelled to propose additional studies to explore the relatedness of primary disease genomes to their matched xenotransplants. We feel that this type of information will contribute substantially to the development of xenotransplants as model systems for studying the basic biology of tumors and for advancing therapy development efforts. Specifically we propose the study of additional trios; matched normal, primary breast tumor and mouse xenograft (primary passage), using our well-developed whole genome shotgun sequencing and analysis. Each trio will be characterized and compared for similarities and differences within the set, then across sets to determine common motifs of enrichment, loss of heterozygosity or amplification/deletion, and so on, between primary disease and xenografts. Due to our existing experience and the fact that we already have produced a genome-wide characterization of the NOD/SCID SNP profile, we should readily be able to analyze these data. Status of Samples: 15 total cases (matched normal, primary breast tumor and mouse xenograft): 45 total genomes. 10 of 15 cases in house. 1 case in resource bank. 2 cases in library construction. 6 cases in data generation. 1 case in analysis. Follow-up work to include validation and extension sequencing. Collaborators: Dr. Matthew Ellis. IRB Status: Compliant.