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
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Citation Impact
MSK Authors
  1. Sam Yoon
    103 Yoon
  2. Meera Hameed
    214 Hameed
  3. Kaled M Alektiar
    298 Alektiar
  4. David Solit
    663 Solit
  5. Leonard H Wexler
    166 Wexler
  6. Narasimhan P Agaram
    158 Agaram
  7. Cristina R Antonescu
    783 Antonescu
  8. Ping Chi
    118 Chi
  9. Mary Louise Keohan
    101 Keohan
  10. Marc Ladanyi
    1196 Ladanyi
  11. Martee L Hensley
    260 Hensley
  12. Mrinal M Gounder
    165 Gounder
  13. Sandra Pierina D'Angelo
    194 D'Angelo
  14. Aimee Marie Crago
    87 Crago
  15. Samuel Singer
    289 Singer
  16. Ahmet Zehir
    313 Zehir
  17. Mark Andrew Dickson
    133 Dickson
  18. Nicholas D Socci
    216 Socci
  19. Michael Forman Berger
    611 Berger
  20. Paul Meyers
    295 Meyers
  21. John H Healey
    506 Healey
  22. Neerav Shukla
    120 Shukla
  23. William Douglas Tap
    258 Tap
  24. Emily Kanaya Slotkin
    42 Slotkin
  25. Brian Untch
    48 Untch
  26. Nikolaus D Schultz
    356 Schultz
  27. Sarah   Chiang
    104 Chiang
  28. Ciara Marie Kelly
    52 Kelly
  29. Benjamin Alexander Nacev
    21 Nacev
  30. Bhumika Jadeja
    4 Jadeja
  31. Timothy Geoffrey Bowler
    8 Bowler
  32. Satshil Rana
    17 Rana
  33. Jason Earl Chan
    13 Chan
  34. Sujana Movva
    17 Movva
  35. Anisha Luthra
    11 Luthra
  36. Hongyu Shi
    5 Shi
  37. Shaleigh Anne Smith
    7 Smith
  38. Azusa Okada
    1 Okada
  39. Jonathan Alexander Strong
    1 Strong
  40. Cerise Tang
    1 Tang