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Sarcoma Study

What is sarcoma?

The term “sarcoma” encompasses a broad family of rare cancers that can affect soft tissue or bone throughout the body, and sometimes both.1 Sarcoma cases constitute about 15% of all cancers in children, but are much rarer in adults and make up only about 1% of adult cancer cases.2

In 2012, it was estimated that about 11,280 Americans would be diagnosed with soft tissue sarcomas and that approximately one third of those people would not survive. In addition, an estimated 2,890 Americans would be diagnosed with bone sarcomas, with approximately half not expected to survive.1

The exact number of people affected is unknown because sarcoma can be misdiagnosed; the disease is difficult to distinguish from other health problems. There are also often few, if any, symptoms at early stages.Additional information on sarcoma.

TCGA focused its study on 6 sarcoma subtypes, including 5 with complex karyotypes:

  • dedifferentiated liposarcoma (DDLPS)
  • leiomyosarcoma (arising in both gynecologic and soft tissue sites) (LMS)
  • undifferentiated pleomorphic sarcoma (UPS)
  • myxofibrosarcoma (MFS)
  • malignant peripheral nerve sheath tumor (MPNST)

and one with simple karyotype:

  • synovial sarcoma (SS)

Sarcoma was part of an effort to characterize rare tumor types.

What have TCGA researchers learned about adult soft tissue sarcoma?

  • Few somatic mutations and numerous copy number changes dominate complex karyotype sarcomas, while gene fusions are a defining feature of simple karyotype sarcoma.

    • TP53, ATRX, and RB1 were among the few genes recurrently mutated across sarcoma types.

    • Copy number alterations frequently occurred in complex karyotype sarcomas, affecting cell cycle and other pathways.

    • SS sarcomas expressed fusions in SSX1 or SSX2 genes and frequently also in TERT.

    • Mutational signatures found in sarcomas are novel, but contain elements of previously described patterns, including those resulting from clock-like mutational processes.

  • In individual sarcoma types, a wide diversity of genomic and regulomic changes associate with patient outcome.

    • For DDLPS, JUN amplification associates with worse survival and should be considered as a therapeutic target.

    • Gynecologic and soft tissue site subtypes of LMS are molecularly distinct enough to support different clinical approaches, but as a whole may benefit from inhibitors of the PI3K-AKT-mTOR pathway.

    • UPS and MFS are molecularly similar despite histological differences and may be driven by alterations in the Hippo pathway.

  • The level of immune infiltration associates differentially with patient outcome for different types of sarcoma.

    • Immune checkpoint inhibitors may be beneficial to certain sarcoma subtypes, such as UPS, MF5, and certain cases of DDPLS.