Cited by 62Sarcoma Diagnosis and TreatmentBone Tumor Diagnosis and TreatmentsCancer Genomics and Diagnostics

Genomics and the Immune Landscape of Osteosarcoma

Wu, Chia-Chin, Livingston, J. Andrew·2020·Advances in Experimental Medicine and Biology

Abstract

Conventional osteosarcoma (OS) is a high-grade intraosseous malignancy with production of osteoid matrix; however, a deeper dive into the underlying genetics reveals genomic complexity and instability that result in significant tumor heterogeneity. While early karyotyping studies demonstrated aneuploidy with chromosomal complexity and structural rearrangements, further investigations have identified few recurrent genetic alterations with the exception of the tumor suppressors TP53 and RB1. More recent studies utilizing next-generation sequencing (NGS; whole-exome sequencing, WES; and whole-genome sequencing, WGS) reveal a genomic landscape predominantly characterized by somatic copy number alterations rather than point/indel mutations. Despite its genomic complexity, OS has shown variable immune infiltrate and limited immunogenicity. In the current chapter, we review the hallmarks of OS genomics across recent NGS studies and the immune profile of OS including a large institutional cohort of OS patients with recurrent and metastatic disease. Understanding the genomic and immune landscape of OS may provide opportunities for translation in both molecularly targeted therapies and novel immuno-oncology approaches.

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Crossref · 10.1007/978-3-030-43085-6_2

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  • The immunosuppressive mechanisms in osteosarcoma include highly mutated and rearranged osteosarcoma genome may not generate sufficient neoantigens to elicit an immune response, aneuploidy and copy number changes alterations, and deregulation of tumor-intrinsic immunosuppressive pathways such as IFNG, MAPK/PI3K/mTOR, and JAK/STAT signal pathways.

    “The immunosuppressive mechanisms in osteosarcoma, including (1) Highly mutated and rearranged osteosarcoma genome may not generate sufficient neoantigens to elicit an immune response, (2) Aneuploidy and copy number changes alterations and (3) Deregulation of tumor-intrinsic immunosuppressive pathways such as IFNG, MAPK/PI3K/mTOR, and JAK/STAT signal pathways [76].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [76]

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Authors
Wu, C.-C., & Livingston, J. A.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Livingston, J. Andrew
Venue
Advances in Experimental Medicine and Biology
Published
2020
Volume
1258
Pages
21-36
ISSN
  • 0065-2598 (ISSN-L)
  • 2214-8019
OpenAlex
W3048320969
Cited by
58
References
83
Citations by year
2026: 4 · 2025: 10 · 2024: 8 · 2023: 16 · 2022: 11 · 2021: 8 · 2020: 1
FWCI
62.06
Type
book chapter
Language
en
Open access
closed
Locations
  • Advances in experimental medicine and biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
osteosarcoma, cancer genomics, tumor immune microenvironment, tumor heterogeneity, somatic copy number alterations, TP53, RB1, aneuploidy, metastatic osteosarcoma, immunogenicity, cancer immunotherapy, targeted therapy
MeSH terms
Bone Neoplasms, Humans, Mutation, Osteosarcoma, Genome, Human, Genomics, DNA Copy Number Variations, High-Throughput Nucleotide Sequencing

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