Document Type

Article

Publication Date

5-6-2025

Identifier

DOI: 10.1038/s41467-025-58678-6; PMCID: PMC12055966

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).

Journal Title

Nat Commun

Volume

16

Issue

1

First Page

4206

Last Page

4206

MeSH Keywords

Humans; Sarcoma; Exome Sequencing; Mutation; DNA Copy Number Variations; Transcriptome; Genomics; Killer Cells, Natural; Female; Male; Gene Expression Profiling

PubMed ID

40328759

Keywords

Sarcoma; Exome Sequencing; Mutation; DNA Copy Number Variations; Transcriptome; Genomics; Natural Killer Cells; Gene Expression Profiling

Comments

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Publisher's Link: https://www.nature.com/articles/s41467-025-58678-6

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