We propose whole genome sequencing and analysis of mouse models and types of mouse tissues that have developed breast cancers representing major subtypes of the human disease. These data will be analyzed and compared to corresponding subtype tumors from human patients.
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: Collaborators Chuck Perou (UNC), Dan Medina and Jeff Rosen (Baylor College of Medicine) have utilized a TP53 -/- mouse model with a BALBc background genome to generate mice that develop breast cancers representing all major subtypes of the human disease, by RNA clustering analysis. These tumors also have been characterized by aCGH in Dr. Perou’s laboratory, and subtype-specific copy number alterations were found. What is missing is a genome-level analysis of sequence changes that lead to the subtype specificity in spite of a shared germline sequence. Goal #1: We propose whole genome sequencing and analysis of the following numbers and types of mouse tissues for this project: 3 tumors of each subtype: Luminal, claudin-low and basal (Total of 9 whole genomes). 1 germline sample from spleen of the BALBc progenitor (Total of 1 whole genome). These data will be analyzed in comparison to corresponding subtype tumors from human subjects, two of which already are completed for basal-like (funded by WUCGI), 50 of which were already sequenced for the luminal subtype (NHGRI and WUCGI funding). Status of Samples: 14 samples total: 3 Luminal, 3 Claudin-low, 4 Basal, 1 Her2, 2 p53null group, and 1 normal germline Balbc progenitor 2 in data generation 12 in quality coverage check Goal #2: In order to round out the subtypes of human breast tumors that correspond to these mouse model tumors, we also propose sequencing two claudin-low cases (UPNs 9830-010384B, 9830-020018B) that will be provided to us by Chuck Perou. He has these samples already in-hand and they are covered under his IRB approval and the dbGaP certification letter already provided by UNC-Chapel Hill. Status of Samples: BRC86 in data generation BRC87 in quality coverage check. Collaborators: Dr. Chuck Perou. IRB Status: Compliant.