We will conduct whole genome sequencing and analysis of mice with serially biopsied colon cancer tumors with known initiating mutations that are sampled as the tumor grows and metastasizes. These data will help build a model that then could be investigated and compared to human colon cancer.
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 will conduct whole genome sequencing and analysis of serially biopsied tumors in the colon cancer model system with known initiating mutations (APC, KRAS) that are sampled as the tumor grows and metastasizes. In general, each mouse will provide 2 or more progression samples, depending upon the specific genetic background. Two goals would be addressed by these progression samples: First, we could identify companion mutations to the known initiating event that occur early in the tumor growth by studying the earliest progression samples. Second, we could identify metastasis-specific mutations by comparisons to the initial tumor genome from the same mouse. These data would help to build a model that then could be investigated in human colon cancer for similarities and differences in terms of genes mutated, or otherwise altered by structural variation. Certainly these data will be informative to TCGA’s ongoing colon cancer sequencing data analyses. Status of Samples: 100 tumors for WGS. These 100 tumors are from the variety of singly mutated knock-out and multiple mutation-carrying mouse models being pursued in the Hung/Kucherlapati lab. We have received 2 cell lines and 1 FFPE to gauge sample quality. The 100 tumors are not in house at this point. Collaborators: Dr. Kenneth Hung, Dr. Chuck Perou. IRB Status: Not applicable (non-human sequencing).