February 7, 2020 @ 12:00 pm – 1:30 pm
Posner Hall 100
5000 Forbes Ave 15213
Mechanisms of oncogene amplification in cancer
Oncogene amplification is a hallmark of many cancers, and cancers with copy number amplifications are often associated with poor outcomes. Despite their importance, the mechanisms causing these amplifications are incompletely understood. In this talk, we describe our recent results suggesting that a large faction of amplification is due to formation of extrachromosomal DNA (ecDNA). EcDNA play a critical role in tumor heterogeneity, accelerated cancer evolution, and drug resistance through their unique mechanism of non-chromosomal inheritance. While predominant, ecDNA are not the only mechanism to cause amplification. In this talk, we describe the genesis of our work on ecDNA, and the computational signatures that help separate ecDNA from other mechanisms including Breakage Fusion Bridge formation, Chromothripsis, but also simpler events such as tandem duplications and translocations. The talk is a mix of published and unpublished work, largely in collaboration with Paul Mischel’s lab at UCSD.