Synapse - Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets

Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets Journal Article

Authors:	Nacev, B. A.; Sanchez-Vega, F.; Smith, S. A.; Antonescu, C. R.; Rosenbaum, E.; Shi, H.; Tang, C.; Socci, N. D.; Rana, S.; Zehir, A.; Gounder, M. M.; Gularte-Merida, R.; Bowler, T. G.; Luthra, A.; Jadeja, B.; Okada, A.; Strong, J. A.; Stoller, J.; Chan, J. E.; Chi, P.; D'Angelo, S. P.; Dickson, M. A.; Kelly, C. M.; Keohan, M. L.; Movva, S.; Thornton, K.; Meyers, P. A.; Wexler, L. H.; Slotkin, E. K.; Bender, J. L. G.; Shukla, N. N.; Hensley, M. L.; Healey, J. H.; La Quaglia, M. P.; Alektiar, K. M.; Crago, A. M.; Yoon, S. S.; Untch, B. R.; Chiang, S.; Agaram, N. P.; Hameed, M. R.; Berger, M. F.; Solit, D. B.; Schultz, N.; Ladanyi, M.; Singer, S.; Tap, W. D.
Article Title:	Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets
Abstract:	Sarcomas are rare tumours with many different subtypes and clinical outcomes; a broader knowledge of their genetic features is required. Here, the authors analyse 2138 soft tissue and bone sarcomas across 45 subtypes using MSK-IMPACT targeted sequencing and find genomic groups that are distinct from histological subgroups. The genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analysis of 2,138 sarcomas representing 45 pathological entities. This cohort is prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations are in cell cycle control and TP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations include TERT amplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varies between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response.
Keywords:	risk; expression; reveals; activation; uterine; blockade; open-label; telomeres; tert promoter mutations; cancer
Journal Title:	Nature Communications
Volume:	13
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2022-06-15
Start Page:	3405
Language:	English
ACCESSION:	WOS:000814803900004
DOI:	10.1038/s41467-022-30453-x
PROVIDER:	wos
PMCID:	PMC9200818
PUBMED:	35705560
Notes:	Article -- 3405 -- Source: Wos