Genomic, transcriptomic, and immunogenomic landscape of over 1300 sarcomas of diverse histology subtypes
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).
Authors
- Michael J. Cavnar (ORCID: https://orcid.org/0000-0002-6197-7945)
- Brooke L. Fridley (ORCID: https://orcid.org/0000-0001-7739-7956)
- John Groundland (ORCID: https://orcid.org/0000-0001-5921-8301)
- Breelyn A. Wilky (ORCID: https://orcid.org/0000-0001-5080-497X)
- Gregory Riedlinger (ORCID: https://orcid.org/0000-0001-5690-7777)
- Bryan P. Schneider (ORCID: https://orcid.org/0000-0003-1868-7739)
- David M. Joyce (ORCID: https://orcid.org/0000-0003-0042-4367)
- Stephen B. Edge (ORCID: https://orcid.org/0000-0002-3285-6191)
- Oliver Hampton (ORCID: https://orcid.org/0000-0001-9164-1070)
- Kenneth Cardona (ORCID: https://orcid.org/0000-0002-8200-3269)
- Gabriel Tinoco (ORCID: https://orcid.org/0000-0002-2565-6124)
- Damon R. Reed (ORCID: https://orcid.org/0000-0002-8238-2465)
- Saman Zeeshan (ORCID: https://orcid.org/0000-0001-9278-6204)
- Andrew Scott Brohl (ORCID: https://orcid.org/0000-0002-0071-0534)
- A.O. Naghavi (ORCID: https://orcid.org/0000-0002-0884-1942)
- Alex C. Soupir (ORCID: https://orcid.org/0000-0003-1251-9179)
- Martin D. McCarter (ORCID: https://orcid.org/0000-0001-8174-1713)
- James L. Chen (ORCID: https://orcid.org/0000-0002-4095-5202)
- John E. Mullinax (ORCID: https://orcid.org/0000-0002-9596-6785)
- Michael D. Radmacher
- Jamie K. Teer (ORCID: https://orcid.org/0000-0003-4513-0282)
- Michelle L. Churchman (ORCID: https://orcid.org/0000-0002-6560-1056)
- Odion T. Binitie (ORCID: https://orcid.org/0000-0002-2674-9939)
- Phaedra Agius (ORCID: https://orcid.org/0000-0002-1688-992X)
- Raphael E. Pollock (ORCID: https://orcid.org/0000-0002-0443-1583)
- Erin M. Siegel (ORCID: https://orcid.org/0000-0003-1779-2510)
- David A. Liebner (ORCID: https://orcid.org/0000-0002-7657-4137)
- Mihaela Druta
- Nathan D. Seligson (ORCID: https://orcid.org/0000-0002-9670-3792)
- Bodour Salhia (ORCID: https://orcid.org/0000-0003-3843-3621)
- George Douglas Letson (ORCID: https://orcid.org/0000-0001-5344-4316)
- Oscar E. Ospina (ORCID: https://orcid.org/0000-0001-5986-4207)
- Benjamin J. Miller (ORCID: https://orcid.org/0000-0002-9319-1795)
- Abdul Rafeh Naqash (ORCID: https://orcid.org/0000-0001-7622-720X)
- Ricardo González (ORCID: https://orcid.org/0000-0003-3853-2582)
- David McKean (ORCID: https://orcid.org/0000-0003-1983-6708)
- Christopher A Moskaluk
- Dale J. Hedges
Institutions
- Rutgers, The State University of New Jersey (US)
- University of Southern California (US)
- University of Iowa (US)
- Indiana University Health (US)
- Roswell Park Comprehensive Cancer Center (US)
- Children's Mercy Hospital (US)
- Emory Healthcare (US)
- University of Kentucky (US)
- Emory University (US)
- University of Utah (US)
- Emory University Hospital (US)
- Huntsman Cancer Institute (US)
- The Ohio State University Wexner Medical Center (US)
- Moffitt Cancer Center (US)
- University of Florida (US)
- USC Norris Comprehensive Cancer Center (US)
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center
- Rutgers Cancer Institute (US)
- University of Oklahoma Health Sciences Center (US)
- University of Virginia (US)
- Indiana University – Purdue University Indianapolis (US)
- University of Missouri–Kansas City (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-06
- DOI
- https://doi.org/10.1038/s41467-025-58678-6
- Citations
- 5
- Primary Topic
- Sarcoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 7.59
Funders
- Moffitt Cancer Center