Fig. 3: Clonal evolution and phylogenetic analysis of LMS tumors.
From: Lineage-defined leiomyosarcoma subtypes emerge years before diagnosis and determine patient survival
a The clinical course of patient Ab17 with a primary (Dx) and two metastatic relapses (MR1 and MR2) is shown (far left, n = 3 samples). Structural variant (SV) overlaps (middle, top) and the cancer cell fraction (CCF) of single-nucleotide variants (SNVs) (middle, bottom) illustrate that there are many SVs and clonal variants that arise independently in the primary tumors and metastatic relapses. Phylogenetic reconstruction of Ab17’s tumors can be seen on the far right. The founder clone harbors a pathogenic TP53 substitution, whole-genome duplication (WGD), as well as loss-of-heterozygosity (LOH) events encompassing TP53 and RB1. The color of each circle represents a distinct clone population. The clonal trajectory and final composition are shown per sample. Branch lengths are proportional to Treeomics mutation assignments. b Rainfall plots of patient Ab17 in diagnosis and their first metastatic relapse illustrate differential kataegis events at different chromosomes between the two time points. Targeted sequencing data were used to confirm kataegis events were unique to each specimen. c The clinical course for patient Ab12 is depicted, which involved no prior treatment and only surgery. The primary specimen at diagnosis (Dx) was located in the inferior vena cava. The tumor was bisected and punch-hole biopsied in three physically distant multiregion (MuRe) locations (n = 3 samples). The phylogenetic reconstruction of this tumor is shown on the right of the schematic and a photo of the resection. The founder clone harbors a pathogenic TP53 substitution, as well as LOH events encompassing TP53, RB1, and PTEN. Larger circles represent major clones, whereas smaller circles represent subclones. The color of each circle represents a distinct clone population. The clonal trajectory and final composition are shown per sample. Branch lengths are proportional to Treeomics mutation assignments, except for clones 8,10 and 6,7 where DPClust mutation assignments were used to stratify the sample.
