Nature Communications (May 2025)
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,
- Raphael Pollock,
- David Liebner,
- James L. Chen,
- Gabriel Tinoco,
- Bodour Salhia,
- Martin McCarter,
- Breelyn A. Wilky,
- Benjamin J. Miller,
- Michael J. Cavnar,
- John S. Groundland,
- Bryan P. Schneider,
- Gregory Riedlinger,
- Stephen B. Edge,
- Christopher A. Moskaluk,
- Kenneth Cardona,
- Abdul Rafeh Naqash,
- Ricardo J. Gonzalez,
- John E. Mullinax,
- David M. Joyce,
- Odion Binitie,
- G. Douglas Letson,
- Arash O. Naghavi,
- Mihaela Druta,
- Damon R. Reed,
- Erin M. Siegel,
- Jamie K. Teer,
- Brooke L. Fridley,
- Andrew S. Brohl
Affiliations
- Alex Soupir
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center
- Oscar E. Ospina
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center
- Oliver Hampton
- Aster Insights
- Michelle Churchman
- Aster Insights
- Michael Radmacher
- Aster Insights
- Dale Hedges
- Aster Insights
- David McKean
- Aster Insights
- Phaedra Agius
- Aster Insights
- Saman Zeeshan
- Department of Biomedical and Health Informatics, School of Medicine, University of Missouri
- Nathan D. Seligson
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida
- Raphael Pollock
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center
- David Liebner
- Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center
- James L. Chen
- Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center
- Gabriel Tinoco
- Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, College of Medicine, The Ohio State University Wexner Medical Center
- Bodour Salhia
- Department of Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles
- Martin McCarter
- University of Colorado School of Medicine
- Breelyn A. Wilky
- University of Colorado School of Medicine
- Benjamin J. Miller
- Department of Orthopaedics and Rehabilitation, University of Iowa
- Michael J. Cavnar
- Department of Surgery, University of Kentucky
- John S. Groundland
- University of Utah, Huntsman Cancer Institute
- Bryan P. Schneider
- Indiana University Simon Comprehensive Cancer Center
- Gregory Riedlinger
- Rutgers Cancer Institute of New Jersey
- Stephen B. Edge
- Roswell Park Comprehensive Cancer Center
- Christopher A. Moskaluk
- Department of Pathology, University of Virginia
- Kenneth Cardona
- Division of Surgical Oncology, Emory University
- Abdul Rafeh Naqash
- Medical Oncology/Phase 1 program, Stephenson Cancer Center, University of Oklahoma Health Sciences
- Ricardo J. Gonzalez
- Sarcoma Department, Moffitt Cancer Center
- John E. Mullinax
- Sarcoma Department, Moffitt Cancer Center
- David M. Joyce
- Sarcoma Department, Moffitt Cancer Center
- Odion Binitie
- Sarcoma Department, Moffitt Cancer Center
- G. Douglas Letson
- Sarcoma Department, Moffitt Cancer Center
- Arash O. Naghavi
- Department of Radiation Oncology, Moffitt Cancer Center
- Mihaela Druta
- Sarcoma Department, Moffitt Cancer Center
- Damon R. Reed
- Department of Individualized Cancer Management, Moffitt Cancer Center
- Erin M. Siegel
- Department of Cancer Epidemiology, Moffitt Cancer Center
- Jamie K. Teer
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center
- Brooke L. Fridley
- Department of Biostatistics and Bioinformatics, Moffitt Cancer Center
- Andrew S. Brohl
- Sarcoma Department, Moffitt Cancer Center
- DOI
- https://doi.org/10.1038/s41467-025-58678-6
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 11
Abstract
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).
