Figure 4: Evolutionary trajectory of BRCA2-mutant and sporadic PCa harbouring IDC.
From: Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories
(a) Subclonal reconstruction of four BRCA2-mutant PCa from microdissected IDC and IC components using CNA and SNV data. (b) Reconstructions of six sporadic PCa with microdissected IDC and IC components using CNA and SNV data. Each tree gives the inferred phylogeny for a single patient. The gray node is the germline. Blue nodes are present in the IC specimen, gold nodes in the IDC specimen, and the relative proportions of each reflect their relative cellular prevalence. Node size reflects the sum of the cellular prevalence of the IDC and IC components. A set of key mutations that occur on each branch are annotated, and the length of the branch is proportional to the number of SNVs that accumulated on it. (c) Early in the development of BRCA2-Mutant PCa, the disease is characterized by amplifications in 3q, MED12, MED12L and MYC, global genomic instability, a global hypomethylation profile and presents as a more aggressive disease. Tumour suppressors appear to be lost early in sporadic PCa, leading to subsequent development of global genome instability, and increased amplifications as the disease advances.
