Fig. 3: Spatial genetic diversity and phylogenetic events predict recurrence.
From: Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer
a,b, Total phylogenetic tree events (two-sided log-rank test, χ2 = 4.9, d.f. = 1; a) and the Spearman metric (two-sided log-rank test, χ2 = 5.7, d.f. = 1; b) predict earlier time to recurrence (n = 106 participants, sequencing cohort IMRT participants with three or more samples with a PGA of ≥0.01). c, Amplification in MYC and/or FGFR1 (coamplified in one participant) predicts earlier time to metastasis (two-sided log-rank test, χ2 = 7.5, d.f. = 1, n = 106 participants). d, Cox proportional hazards (CPH) model of time to recurrence using clinical covariates and number of low-pass WGS samples with CNAs. Three metrics significant in a univariate CPH model (P < 0.1) are also included in the model (natural log of lossness, total phylogenetic events split by median value and Spearman). The forest plot shows 95% CI of HRs and the covariate P values, derived from a Wald test (n = 106 participants, *P < 0.05, **P < 0.01, ***P < 0.001). HRs for lossness and Spearman represent the increase in hazard between their 5th and 95th percentile values (within the sequencing cohort). e, mPGA per participant in primary samples (n = 109 participants) compared to the mPGA of individual relapse samples (n = 9 samples, two-sided Mann–Whitney U-test, W = 962). f–i, Phylogenetic analysis of primary and relapse samples (cfDNA) taken at recurrence. Tips of tumor nodes represent either the automated classifier ISUP grade group (primary diagnostic biopsies) or a cfDNA sample (red). Time since the diagnostic biopsy is labeled next to the cfDNA nodes in years (yrs). Representative copy number profiles are shown for a single cfDNA sample and the primary diagnostic biopsy that is most related to the cfDNA. Edges are labeled with phylogenetic events plus specific CNA events (for example, whole-genome duplication (WGD) or gene amplification (amp)) or detected point mutations. Genes present in the diagnostic biopsy panel are highlighted in bold and may be detected in both the primary and relapse samples. Genes not in bold are only detectable in the relapse samples and may also be present in the diagnostic biopsies. Below each tree, the timeline shows treatment history. Each event is rounded to the nearest 6 months. Each square represents a year. Treatment descriptions are written in shorthand; Abi, abiraterone acetate; Cab, cabazitaxel; CN, copy number; Dex, dexamethasone; Doce, docetaxel; Enza, enzalutamide; Ra-223, radium-223; RT, radiotherapy; Salv. HiFU, salvage high-intensity focused ultrasound; VAF, variant allele frequency.
