DR-230 The impact of genomic alterations in breast cancer pathogenesis

HER2-positive breast cancer is an aggressive subtype driven by amplification of the Her2/Erbb2 gene. This oncogene is amplified and implicated in chromothripsis, a catastrophic event that causes massive genomic rearrangements. Characterizing chromothripsis in HER2-positive breast cancer and other aggressive subtypes of disease is an important step towards improved understanding of the etiology of disease. We will use whole-genome sequencing data to identify structural rearrangements at single nucleotide resolution and infer mechanisms of chromosome shattering and repair. We hope to understand whether chromothripsis associated with poor outcome in HER2-positive breast cancer and other aggressive subtypes of breast cancer, as well as to evaluate its prevalence in metastatic vs. non-metastatic tumors, and the impact of treatment on genomic aberrations.

Christina Curtis, Stanford University School of Medicine, USA