Allelic Selection of Amplicons in Glioblastoma Revealed by Combining Somatic and Germline Analysis

• DOI: 10.1371/journal.pgen.1001086
• Publication Date: 2010-09-02T16:03:54Z
• Authors: Thomas LaFramboise; Ninad Dewal; Katherine Wilkins; Itsik Pe'er; Matthew L. Freedman
• Keywords: Amplicon

Cancer is a disease driven by combination of inherited risk alleles coupled with the acquisition somatic mutations, including amplification and deletion genomic DNA. Potential relationships between aspects have only rarely been examined on genome-wide level. Applying novel integrative analysis SNP copy number measurements, we queried tumor normal-tissue genomes 178 glioblastoma patients from Genome Atlas project for preferentially amplified alleles, under hypothesis that oncogenic germline variants will be selectively in environment. Selected are revealed allelic imbalance across samples. This general approach based genetic principles provides method identifying important tumor-related alleles. We find most significantly overrepresented amplicons tend to occur genes involved regulation kinase transferase activity, many these known contributors gliomagenesis. The also implicates synapse genes. By incorporating gene expression data, demonstrate synergy preferential DOCK4 EGFR. Our results support notion combining data can identify regions relevant cancer biology.