A systems biology approach to study high-grade osteosarcoma

Kuijjer, M.L. (2013)

Doctoral Thesis

High-grade osteosarcoma is a primary bone tumor with complex genetic alterations, for which targeted therapy is lacking. The aim of this thesis was to use high-throughput molecular data analysis of high-grade osteosarcoma specimens and model systems, in order to learn more on osteosarcomagenesis and to find possible ways to inhibit this process. By analyzing different microarray data types using a systems biology approach, genomic instability was identified as an important driver of osteosarcomagenesis. A protective role of macrophages against metastasis of osteosarcoma was detected. In addition, the IR/IGF1R and PI3K/Akt signaling pathways were discovered as potential targets for treatment. This thesis provides the first steps in unraveling the genomic and transcriptomic landscape of high-grade osteosarcoma, and provides a biological rationale for certain new options for adjuvant treatment of this highly genomica lly unstable tumor.

• High-throughput
• Data integration
• Data analysis
• Microarray
• Computational biology
• Sarcoma
• Cancer
• Biomedicine
• Systems biology
• High-grade osteosarcoma
• Osteosarcoma
• Bioinformatics

• All authors: Kuijjer, M.L.
• Supervisor: Hogendoorn, P.C.W.
• Co-supervisor: Cleton-Jansen, A.M.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2013-06-26
• Sponsorship: Nederlandse Kankerbestrijding KWF