Role and Mechanism of Structural Variation in Progression of Breast Cancer

As part of a large cohort of cancer samples we analyzed structural variants and their mechanism from a set of 12 basal type Breast invasive carcinomas (BRCA) We were able to identify a total of 1,657 high confidence breakpoints in the breast cancer datasets. Of the 154 complex mutations (CGRs), BRCA samples had 19. Although these were almost equally divided between one- off events and stepwise events, none of the BRCA samples showed evidence for chromothripsis. MMBIR and/or MMEJ are less common in tumors than in germline lineages, and CGR breakpoints are significantly depleted for microhomology relative to simple SV breakpoints. Using ploidy- seq and next generation sequencing, on tumor sample from a 59- year- old triple negative breast cancer patient, we can study chronology of mutations in a tumor sample, and begin to get a handle on the extensive tumor heterogeneity. Preliminary data suggests that very few mutations were shared between the different sub- populations in a tumor. We also have data that suggests that in the case of this one patient sample, the genome evolved from the normal diploid state into a hypodiploid state, which then further evolved into two highly amplified states after a genome doubling event.