Fig. 4

Landscape of PD-specific genomic alterations. A Stacked bar plots comparing the prevalence of genomic alterations at BL vs. PD for key BC genes. Colors represent the different genomic alterations including WT, missense, frameshift, inframe deletion, nonsense (splice site mutation, germline mutation) copy number amplification, copy number deletion, fusion, and mixed, indicating the tumor harbored multiple alterations. B Oncoprint of the mutational profile of selected genes for patients with paired baseline/on-treatment and PD samples. Paired samples for the same patient grouped together to highlight PD-specific alterations. Patients ordered by PFS as indicated by the track above the oncoprint. Colors represent the different mutation types. Stacked bar plots and number on the right show the number of patients with PD-specific alterations, with the percentage in parenthesis indicating the frequency of PD-specific alternations in 21 patients. C PD-specific RB1 mutations from our cohort in comparison with the spectrum of RB1 mutations reported in the PALOMA-3 study. We observed 6 mutations from 23.8% (5/21) of patients. Comparing longitudinal changes in RB1 TARGETS (D) and ESTROGEN RESPONSE EARLY signatures (E) between paired BL and PD tumors among the three groups. RB1 LOF: patients harboring PD-specific RB1 loss-of-function genomic alterations at PD. ESR1 GOF: patients harboring PD-specific ESR1 gain-of-function genomic alterations at PD. Other: all other patients with paired BL and PD samples. Patient BRO7F-093 harbored acquired mutations in both RB1 and ESR1 and was included in the “RB1 LOF” group in D and “ESR1 GOF” group in E. RB1 TARGETS: EGUCHI CELL CYCLE RB1 TARGETS gene set from mSigDB v5.2