Fig. 1: Genomic differences and normal cellular lineages of LMS transcriptional subtypes.

a Principal Component Analysis (PCA) of LMS transcriptomes (n = 79 TCGA RNA-seq and n = 51 Toronto RNA-seq) leads to three defined subtypes of LMS, in which segregation is broadly influenced by anatomical location. While subtype 1 is a mix of all sites (extremity, abdominal and gynecological), subtype 2 is largely abdominal, with some extremity tumors. Subtype 2 can be further sub-stratified into subtype 2a and 2b. The metastatic lesions in subtype 2 cluster with their matched primary tumors. There are two metastatic tumors in subtype 1 that are from the same patient. Lastly, subtype 3 represents a largely gynecological (uterine, vaginal, fallopian tube) subtype. b Genomic point mutation, indel (insertion/deletion), and structural variant (SV) burdens are lower in subtype 2 than subtypes 1 or 3. Horizontal black lines represent the median values for each subtype. Source data are provided in Supplementary Data 7. c LMS molecular subtypes are of distinct smooth muscle lineages: vertices of the triangular plot represent smooth muscle of vasculature, digestive tissue, and gynecological tissue. Individual dots represent LMS cancers and where they lie in the cluster. Adjacent contour plots illustrate density distribution of LMS molecular subtypes. d Uniform Manifold Approximation and Projection (UMAP) illustrates clustering of 271 muscle-related GTEx normal tissue types (from the Genotype-Tissue Expression Program) and 130 LMS reveals distinct smooth muscle lineages of LMS subtypes. e Boxplots represent the expression (in transcripts per million, TPM), for smooth muscle (SM) genes: LMOD1 (leiomodin 1), MYOCD (myocardin), DES (desmin), and CALD1 (caldesmon) are key smooth muscle genes that are commonly expressed in LMS. The boxes represent the 25th and 75th percentile (bottom and top of box), and median value (horizontal band). The whiskers indicate the variability outside the upper and lower quartiles. These genes are highly expressed in vascular (n = 110), digestive (n = 119), and gynecological (Gyn., n = 42) normal smooth muscle. Genes are also expressed in subtype 2 (n = 85) and subtype 3 (n = 22) LMS, but not as highly in LMS subtype 1 (n = 23).