An Exploration of the Medulloblastoma and Glioblastoma Genomes: A Critical Analysis of Candidate Cancer Genes as Potential Molecular Targets for Diagnostics and Therapeutics
Background
Cancer is a genetic disease caused by sequential accumulation of mutations in oncogenes and tumor suppressor genes. The identification and characterization of such mutations has enabled the development of molecular diagnostics as well as targeted molecular therapies which have been utilized to achieve remarkable clinical benefit in the treatment of specific tumor types. The vast majority of genetic alterations causing most human cancers remain unknown, however, as demonstrated by the results of our recent analysis of the breast and colon cancer genomes, which revealed a remarkable level of mutational complexity within these two tumor types. This analysis identified a number of candidate cancer genes, the majority of which had not previously been linked to neoplasia.
Project Goals
The objective of this study is to analyze a large panel of medulloblastomas and glioblastomas for alterations in a select group of candidate cancer genes, with an ultimate goal of rapidly identifying specific genes and pathways which may serve as targets for novel molecular diagnostics and therapies in these tumor types. This will specifically be accomplished by integrating the results of DNA sequencing-based mutation analyses of the selected candidate cancer genes with gene copy number data obtained on the same panel of brain tumors using high-density SNP genotyping. A systems analysis of the combined mutation and gene copy number data will be conducted in order to select the most potentially clinically relevant genes, functional groups, and genetic pathways for further study. Finally, enotype:phenotype analysis of any commonly mutated genes will be performed, including their relation to medulloblastoma histologic subtype and patient outcome as well as glioma histologic grade.
