Multi-Omic Assessment of Oncogenic PIK3CA Mutations Using Isogenic Cell Line Models

Abstract

In this dissertation, I demonstrate the utility of combining the discovery tools of iso- genic cell lines and molecular profiling by sequencing. This dissertation outlines findings made through the application of multiple sequencing techniques used on isogenic cell line models of hotspot PIK3CA breast cancer mutations. The current state of targeted treatment for PIK3CA mutant breast cancer is lacking and new discoveries are needed to improve upon this. Our findings elucidate many distinct differences in cell signaling caused by these mutations, and also highlight potential mutation-preferential targets of treatment that can be used to improve upon current treatment paradigms for PIK3CA-mutant breast can- cer. The results of this work build upon our understanding of these independent mutations and provide a framework for future study of oncogenic mutations using functional genomic analyses.