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Introduction to Glioblastoma
Chris PlaisierIntroduction to Systems Biology Course
Institute for Systems Biology
Systems Level Integration
• Integration of high-throughput technologies is a common practice in systems biology
• In these tutorial sections we will explain and then have a hands-on time to get experience working with high-throughput data
• Tutorials will focus on the deadly brain cancer glioblastoma multiforme or glioma
Glioma: A Deadly Brain Cancer
Wikimedia commons
Glioma Survival
http://www.neurooncology.ucla.edu/
5 years
10 years
Grade I Grade II Grade III Grade IV
Neurophysiology
Heterogeneity of Tumors
Mischel et al, 2004
Hallmarks of Cancer
Hanahan et al. 2000
Parallel Pathways of Tumorigenesis
Hanahan et al. 2000
Acquisition of hallmarks may vary mechanistically and chronologically:
Can Genome-Wide Profiles Inform Cancer Treatment Planning?
Individual genome-wide profiles are sorted
Colon cancer patients
Have mutated K-ras gene
Profile A...give targeted
therapy A
Respond to targeted therapy A
Do not have mutated K-ras gene
A E A
A
AEE
E
B C C
B C
B
BC
B C
B C B
Utility of Patient Stratification
Mischel et al, 2004
Genome-Wide Profiling: Many Ways
miRNAs in Cancer
Caldas et al., 2005
RISC
miRNAs are Dysregulated in Cancer
Chan et al., 2011
Copy Number Variation
• Compare normal tissue vs. cancerous
• Amplifications
• Deletions
• Translocations
wikipedia.org
Oncogene Amplification
http://www.cambridgebluegnome.com/copy_number_imbalance
miRNAs are Trans-Acting Factors
Gene Expression
http://www.news-medical.net/health/What-is-Gene-Expression.aspx
Stratification of Patients
Mischel et al, 2004
Utility of miRNAs in Cancer
Chan et al., 2011