Table 1.
Summary of genomic studies in leiomyosarcoma.
| Ref. | Modality | Total n | STLMS | ULMS | Major Findings | TP53 | RB1 | ATRX | CDKN2A | CDKN2B | PTEN | Other |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| [16] | WES | 80 | 53 | 27 | Predominantly chromosomal or arm-level deletions. | Mutation, 50%; deep deletion, 9% | Deep deletion, 14% | Deep deletion, 14% | Deep deletion, 13% | |||
| [17] | Targeted exome (230 genes) | 35 | 35 | 0 | Losses of chromosomal regions involving key tumor suppressor genes PTEN (10q), RB1 (13q), CDH1 (16q), and TP53 (17p) were the most frequent genetic events. Gains mainly involved chromosome regions 17p11.2 (MYOCD) and 15q25-26 (IGF1R). | Mutation, 37%; deletion, 43% | Mutation, 8.5%; deletion, 54% | Deletion, 60% | CDH1 deletion, 46% | |||
| [18] | Targeted exome (47 genes) | 751 | 350 | 401 | TP53 mutations in 42.2% of STLMS and 40.5% of ULMS, BRCA2 mutations in 11% of STLMS and 21.7% of ULMS. PTEN mutations in 6.3% of STLMS and 0% of ULMS. | Mutation, 41.7% | Mutation, 5.3% | Mutation, 4.4% | BRCA2 mutation, 17.1% | |||
| [19] | SNP arrays, RNA seq, WGS on subset | 84 | 0 | 84 | Alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the majority of ULMS. Enrichment in PI3K/AKT/mTOR, estrogen-mediated S phase entry, and DNA damage response signaling pathways. | Altered in 92%; mutation, 41.7%; deletion, 33% | 88% | 75% | Mutations in MED12, 12.5%; EIF3A, 16.7%; ABL1, 12.5%, IGF2R, 12.5%; ATR, 8.3%; RAD50, 8.3%. BRCA1, 8.3%. | |||
| [20] | WES | 49 | 39 | 10 | Notable mutational heterogeneity, near-universal loss of TP53 and RB1, widespread DNA copy number alterations with evidence of chromothripsis, and frequent whole-genome duplication. | 49% | 27% | 24% | 57% | |||
| [21] | WES | 19 | 0 | 19 | TP53, MED12, and ATRX mutations were prevalent. | 33% | 26% | MED12, 21% | ||||
| [22] | Targeted exome (151 genes) | 25 | 16 | 9 | CNVs were identified in 85% of cases. Most frequent losses in chromosomes 10 and 13 including PTEN and RB1. Most frequent gains in chromosomes 7 and 17. | 36% | 12% | 16% | ATM, 16%; EGFR, 12% | |||
| [23] | Targeted exome (341–468 genes) | 80 | 0 | 80 | Compared to ESS, STUMP. PTEN alteration frequency was higher in the metastases samples as compared with the primary samples. Genomes of low-grade tumors were largely silent, while 50.5% of high-grade tumors had whole-genome duplication. | 56% | 51% | 31% | ||||
| [24] | WGS | 53 samples (34 patients) | 23 | 11 | Mutational signatures highlight importance of DNA damage repair and homologous recombination deficiency. Dystrophin deletion associated with worse outcome. Whole-genome doubling was prevalent. Analysis of matched primary-metastatic samples suggested divergence 10–30 years prior to diagnosis. | Mutation, 82.3%; deletion, 14.7% | Mutation, 11.8%; deletion, 8.8% | Deletion, 8.8% |
WES, whole exome sequencing. WGS, whole genome sequencing. SNP, small nucleotide polymorphism.