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Genomic, transcriptomic, and immunogenomic landscape of over 1300 sarcomas of diverse histology subtypes
Journal article   Open access   Peer reviewed

Genomic, transcriptomic, and immunogenomic landscape of over 1300 sarcomas of diverse histology subtypes

Alex Soupir, Oscar E. Ospina, Oliver Hampton, Michelle Churchman, Michael Radmacher, Dale Hedges, David McKean, Phaedra Agius, Saman Zeeshan, Nathan D. Seligson, …
Nature communications, Vol.16(1), 4206
05/06/2025
DOI: 10.1038/s41467-025-58678-6
PMCID: PMC12055966
PMID: 40328759
url
https://doi.org/10.1038/s41467-025-58678-6View
Published (Version of record) Open Access

Abstract

Given their rarity and diversity, a fundamental understanding of the genomic underpinnings for many sarcoma subtypes is still lacking. To better define the molecular landscape of this group of diseases, we perform matched whole exome sequencing and RNA sequencing on a cohort of 1340 sarcoma tumor specimens. We identify recurrent somatic mutations and observe an increased mutational burden in metastatic vs. primary samples ( p  < 0.001). We observe frequent copy number alterations including whole genome doubling, with this feature being more common in metastatic tumors (p = 0.026). Estimation of immune cell abundances followed by hierarchical clustering identifies five immune subtypes ranging from low to high and we observe inferior overall survival in immune deplete clusters compared to immune enriched ( p <  0.01). Interestingly, GIST predominantly form a distinct “immune intermediate” cluster that is marked by a specific enrichment for NK cells (FDR < 0.01). Sarcoma is a highly heterogeneous disease, which can be caused by a large variety of mutations. Here, the authors utilise multi-omics to characterise a cohort of 1,340 sarcoma tissue specimens to identify key somatic mutations and identify immune subtypes.

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