CGCI developed the Medulloblastoma Project to apply newly emerging genomic methods towards the discovery of novel genetic alterations in medulloblastoma (MB). MB is the most common malignant brain tumor in children, accounting for approximately 20% of all pediatric brain tumors. Despite significant progress in treatment over the last several decades, about 50% of MB patients do not live more than 5 years after diagnosis. Moreover, current treatment of the disease is very aggressive, oftentimes causing serious long-term neurological side effects. To improve survival and quality of life of MB patients, new therapeutic strategies must be developed.
CGCI investigators examined a number of MB tumors using high-density microarrays and Sanger sequencing. Their bioinformatics analysis uncovered several frequently altered genes not previously identified in MB, many of which have significant biological implications. Further analysis revealed the alteration profiles between pediatric and adult tumors are different, suggesting the initiation and progression of pediatric and adult cancers is likewise different. The completion of this project opens new doors for research and is an initial step towards finding improved therapeutic strategies for patients suffering from medulloblastoma.
The MB Project has completed all phases of the timeline.
This medulloblastoma study is complete, and content will not change. Please refer to the publication.
Visit the CGCI Overview page to learn more about the general timeline of CGCI projects.
CGCI investigators performed two phases of genome-wide analysis, the initial “Discovery Screen” followed by the “Prevalence Screen,” to determine genes that were frequently altered in MB tumors.
Discovery Screen
Investigators searched for single-base mutations and small insertions or deletions by Sanger sequencing of over 20,000 protein-coding and 715 microRNA genes. They also searched for alterations in copy number using high-density microarrays. They verified the tumor-specific association of each mutation by re-sequencing these genes using either Illumina GAII or Sanger sequencing.
Samples
22 pediatric MB samples total (below), with 1 matched normal blood sample
- 17 primary tumors
- 4 xenograft mouse models
- 1 cell line
Genomic Methods
- Protein-coding and microRNA Gene Sequencing (Sanger)
- Copy Number Analysis (SNP arrays)
Prevalence Screen
Investigators sequenced genes that were frequently mutated in the discovery screen to determine the frequency of each mutation in a larger cohort of MB tumors (66 pediatric and adult tumors). They also analyzed the sequencing data with bioinformatic algorithms to predict which mutations were likely to disrupt protein function.
Data from the medulloblastoma study are archived.