Fig. 4

Schematic of tumor evolution. The history of tumor evolution in each patient is modeled as a subclonal hierarchy inferred from the somatic mutations and large scale genomic regions harboring loss of heterozygosity (LOH features) using the SCHISM framework, and is depicted as a tree. Each tree starts from a root node corresponding to the normal fallopian tube epithelium (germline). In all patients, mutations in TP53 (red boxes) are among the earliest somatic alterations and are ubiquitously present in all tumor samples. Somatic alterations (boxes) are acquired along edges (arrows) of the tree, and example alterations are indicated in each case. Nodes of the tree represent cells whose genotype is described by the presence of somatic mutations and LOH features on the path connecting the node to the root of the tree. Each node is labeled with tumor samples harboring all upstream and lacking any downstream alterations. The trees inferred for all patients support a pattern of evolution with p53 signatures and STIC lesions as early events in tumorigenesis. Mutation clusters and LOH feature groups follow the same color code as Fig. 2