Table 2.

Summary of transcriptomic studies in leiomyosarcoma.

Ref.	Total n (LMS)	STLMS	ULMS	Modality	Major Findings
[16]	80	53	27	Bulk RNA sequencing	Identified three subgroups: ULMS group with poor prognosis and two STLMS clusters (C1, C2). C1 with hypermethylation, higher expression of IGF1R and cell cycle control genes, DNA replication, DNA repair, RB1 mutations, PTEN deletion. C2 with more inflammatory cells (NK and mast).
[20]	49	39	10	Bulk RNA sequencing	Identified three subgroups. Subgroup 1 with platelet degranulation, complement activation, and metabolism signatures. Subgroup 2 with muscle development and regulation of membrane potential signatures. Subgroup 3 with myofibril assembly, muscle filament function, and cell–cell signaling signatures.
[40]	51	35	16	Microarray	Identified three subgroups. Subgroup 1 with muscle contraction and actin cytoskeleton genes. Subgroup 2 with protein metabolism, cell proliferation, and organ development genes. Subgroup 3 with CSF1 response genes.
[42]	99	50	49	Bulk RNA sequencing	Identified three subtypes. Validated their findings from Beck et al. study using new cohort (n = 99) and TCGA data (n = 82). Identified IHC-compatible assays for different STLMS subtypes.
[19]	24	0	24	Bulk RNA sequencing	Enrichment in PI3K/AKT/mTOR, estrogen-mediated S phase entry, and DNA damage response signaling pathways.
[39]	40			Microarray	Identified a muscle gene-enriched group of 11. Remaining 29 were heterogeneous.
[41]	17			Microarray	No difference among anatomic site, tumor grade, or metastatic lesions. ULMS enriched for site-specific genes such as regulators of urogenital differentiation, development, and growth (ESR1, HOXA10, PBX1, and FAT) compared to STLMS.
[24]	113 (130 samples, 51 newly sequenced, 79 from TCGA)	23	11	Bulk RNA sequencing	Identified three subtypes. Subtype 1 contained LMS from different anatomic sites, harbored higher TMB, and was associated with worse OS and DSS. Subtype 2 was mostly abdominal and was associated with better OS and DSS compared to the other subtypes. Subtype 3 was mostly uterine, harbored higher TMB, and was associated with worse OS and DSS. Matching primary-metastatic samples allowed for assessing tumor evolution; metastases maintained subtype.