Sarcoma Basic Science

Basic Science
Understanding basic biology is the key to new treatments and to understanding the behavior of these fascinating diseases. Over the past few years there has been a lot of investigation into these tumours and our understanding is improving. New technologies like whole-genome sequencing have helped us to understand that in fact sarcomas are a group of diseases, each with their own idiosyncrasies.

Bone and soft tissue tumours are such a diverse group of neoplasms that understanding their biology is an incredibly complex task. Nonetheless, significant advancements are being made that are helping us to refine our current treatments and develop new therapies for the future. Understanding how each of these tumours behaves and responds is essential to planning effective treatment, and this complexity is one of the reasons these tumours are often managed in specialist units.



  • Thought to arise from cells of mesenchymal lineage
    • Recapitulate tissues of mesenchymal origin
  • Cells display the hallmarks of cancer as outlined by Hanahan and Weinberg
    • Self-sufficiency in growth signals
    • Insensitivity to anti-growth signals
    • Evasion of programmed cell death
    • Limitless replicative potential
    • Sustained angiogenesis
    • Tissue invasion and metastasis

Genetics and Molecular Biology

Two major groups

  1. Those characterized by complex karyotypic abnormalities (2/3)
    • Numerous chromosomal changes that appear random and highly extensive
    • Some genes frequently involved, such as TP53
    • Examples: Pleomorphic undifferentiated sarcoma, angiosarcoma, osteosarcoma
  2. Those with simple karyotypic changes (1/3)
    • Characteristic recurring genetic abnormalities including translocations, amplifications/deletions or mutations
    • Diagnostically important as they are pathognomonic
    • Therapeutically can represent targets for drugs (e.g. Imatinib targeting KIT/PDGFR-mutant gastrointestinal stromal tumours)


  • Differs between subtypes
    • Low grade with high potential for local recurrence
    • High grade with high potential for systemic metastasis
  • May change over time
    • E.g. dermatofibrosarcoma protuberans can undergo fibrosarcomatous change
  • Ability to differentiate between types is important for treatment
    • Use of molecular techniques for diagnostic genetic changes is increasingly important



  • GIST and Imatinib
    • Gastro-intestinal stromal tumour (GIST) is a tumour of the GI tract
    • Receptor mutation¬†KIT/PDGFR¬†identified
    • Imatinib is a tyrosine-kinase inhibitor developed to target this receptor
    • Imatinib has been shown to prolong life in patients with GIST