Abstract 796: Utilizing TCRβ and whole exome sequencing to determine the clonality and mutational spectrum of p53-null thymic lymphomas.

Abstract

Abstract The tumor suppressor p53 is nonfunctional in over 50% of cancers. The ability for p53 to protect the cell from tumorigenesis is rooted in its ability to induce cell cycle arrest, apoptosis, and senescence following genotoxic stress. Furthermore, loss of p53 in mice gives rise to spontaneous thymic lymphomas and sarcomas. In this study, we used the p53-KO mouse as a model for progression of tumorigenesis. We first analyzed genomic DNA of p53-KO and WT normal thymus at various ages using TCRβ sequencing. This procedure allowed us to determine the clonality of the T cell repertoire. We then analyzed the clonality of p53-KO thymic lymphomas. Our results indicated that while the highest T cell clone was 0.08% for normal thymus, the highest T cell clone for the p53-KO tumor was 70%, indicating that the p53-KO thymic lymphomas were monoclonal. Building on this data, we analyzed the mutations occurring in the thymic lymphomas by mouse exome sequencing. We believe that combining TCRβ sequencing with mouse exome sequencing will allow for a better understanding of the clonality and genetic mutations required for cellular transformation. Citation Format: Crissy Dudgeon, Chang Chan, Yvonne Sun, Arnold J. Levine. Utilizing TCRβ and whole exome sequencing to determine the clonality and mutational spectrum of p53-null thymic lymphomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 796. doi:10.1158/1538-7445.AM2013-796