Abstract IA17: Deciphering cancer genome evolution in heterogenous tumors

Abstract

Abstract Cancer drug resistance is almost inevitable in the majority of patients with advanced metastatic tumors. Intratumor heterogeneity, facilitating rapid tumor evolution, is one of the main causes of tumor adaptation and resistance to cancer therapies. In this talk I will explore how cancer genome sequencing data can shed light on diversity within tumors and the processes shaping cancer genome evolution over space and time. Harnessing both extensive multi-region and single-sequencing data we have investigated intra-tumor heterogeneity across 10 major cancer types, focusing on non-small cell lung cancer, clear cell renal cell carcinoma, and esophageal adenocarcinoma. I will discuss our findings shedding light on the extent to which mutations in known driver genes, and “actionable mutations,” linked to targeted therapies, are clonal or subclonal. Tumor phylogenies and whether patterns of tumor evolution can be deciphered in these cancer types will also be explored. Temporal dissection of mutational signatures across cancer types will be used to reveal the dynamics of mutational processes during tumor evolution. I will explore how APOBEC mediated-mutagenesis can be linked to branched tumor evolution, and the acquisition of subclonal driver events across cancer types. Finally, the challenges and clinical implications of intratumor heterogeneity will be discussed. Citation Format: Nicholas McGranahan. Deciphering cancer genome evolution in heterogenous tumors. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr IA17.