Early Breast Cancer Evolution by Autosomal Broad Copy Number Alterations

Abstract

The availability of comprehensive genomic datasets across patient populations enables the application of novel methods for reconstructing tumor evolution within individual patients. To this end, we propose studying autosomal broad copy number alterations (CNAs) as a framework to better understand early tumor evolution. We compared the broad CNAs and somatic mutations of patients with 1 to 10 autosomal broad CNAs against the full set of patients, using data from The Cancer Genome Atlas breast cancer project. We reveal here that the frequency of a chromosome arm obtaining a broad CNA and a genome acquiring somatic mutations changes as autosomal broad CNAs accumulate. Therefore, we propose that the number of autosomal broad CNAs is an important characteristic of breast tumors that needs to be taken into consideration when studying breast tumors. To investigate this idea more in-depth, we next studied the frequency that specific chromosome arms acquire broad CNAs in patients with 1 to 10 broad CNAs. With this process, we identified the broad CNAs that exhibit the fastest rates of accumulation across all patients. This finding suggests a likely order of occurrence of these alterations in patients, which is apparent when we consider a subset of patients with few broad CNAs. Here, we lay the foundation for future studies to build upon our findings and use autosomal broad CNAs as a method to monitor breast tumor progression in vivo to further our understanding of how early tumor evolution unfolds.