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Updated: Jun 24, 2026
Methods to Enable Spatial Transcriptomics of Bone Tissues
Published on: May 3, 2024
Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated
Bekim Sadikovic1, Maisa Yoshimoto, Susan Chilton-MacNeill
1Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada M5G 1X8.
Abstract:
Altered gene expression in tumors can be caused by copy number alterations to DNA or mutation affecting coding or regulatory regions of genes. However, epigenetic events may also influence gene expression. Malignant cells can show major disruptions in DNA methylation profiles, which are manifested as aberrant hypermethylation or as hypomethylation of gene promoters, as well as global genomic hypomethylation. In this study we performed integrative whole-genome analysis of DNA copy number, promoter methylation and gene expression using 10 osteosarcomas. We identified significant changes including: hypomethylation, gain, and overexpression of histone cluster 2 genes at chromosome 1q21.1-q21.3; loss of chromosome 8p21.2-p21.3 and underexpression of DOCK5 and TNFRSF10A/D genes; and amplification-related overexpression of RUNX2 at chromosome 6p12.3-p21.1. Amplification and overexpression of RUNX2 could disrupt G2/M cell cycle checkpoints, and downstream osteosarcoma-specific changes, such as failure of bone differentiation and genomic polyploidization. Failure of DOCK5-signaling, together with p53 and TNFRSF10A/D-related cell cycle and death pathways, may play a critical role in abrogating apoptosis. Our analyses show that the RUNX2 interactome may be constitutively activated in osteosarcoma, and that the downstream intracellular pathways are strongly associated with the regulation of osteoblast differentiation and control of cell cycle and apoptosis in osteosarcoma.
Insights
Osteosarcoma gene expression is altered by DNA copy number changes and epigenetic events like DNA methylation. RUNX2 amplification and overexpression disrupt cell cycle and differentiation, impacting osteosarcoma development.
Area of Science:
- Genomics
- Epigenetics
- Cancer Biology
Background:
- Gene expression in tumors is influenced by DNA copy number alterations, mutations, and epigenetic events.
- Malignant cells exhibit disrupted DNA methylation profiles, including promoter hypermethylation/hypomethylation and global genomic hypomethylation.
- Osteosarcoma is a primary bone cancer characterized by genetic and epigenetic dysregulation.
Purpose of the Study:
- To perform an integrative whole-genome analysis of DNA copy number, promoter methylation, and gene expression in osteosarcoma.
- To identify key genetic and epigenetic alterations driving osteosarcoma development and progression.
- To elucidate the functional consequences of identified alterations on cellular pathways.
Main Methods:
- Integrative whole-genome analysis.
- Analysis of DNA copy number, promoter methylation, and gene expression data.
- Utilized data from 10 osteosarcoma samples.
Main Results:
- Identified hypomethylation, gain, and overexpression of histone cluster 2 genes at 1q21.1-q21.3.
- Observed loss of 8p21.2-p21.3 and underexpression of DOCK5 and TNFRSF10A/D genes.
- Found amplification-related overexpression of RUNX2 at 6p12.3-p21.1, potentially disrupting cell cycle and differentiation.
Conclusions:
- RUNX2 amplification and overexpression may drive osteosarcoma by disrupting cell cycle checkpoints and osteoblast differentiation.
- Dysregulation of DOCK5, p53, and TNFRSF10A/D pathways may inhibit apoptosis.
- The RUNX2 interactome appears constitutively activated in osteosarcoma, influencing differentiation, cell cycle, and apoptosis.
