An Integrated Genomic Analysis of Human Glioblastoma Multiforme

TLDR

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs. We sequenced 20,661 protein‑coding genes, determined amplifications and deletions using high‑density oligonucleotide arrays, and performed gene expression analyses with next‑generation sequencing technologies in 22 human tumor samples. The study uncovered numerous previously unrecognized genetic alterations in GBM, including recurrent IDH1 mutations in 12 % of patients—particularly young and secondary GBM cases—associated with improved overall survival, underscoring the value of unbiased genomic analyses for classification and targeted therapy.

Abstract

Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleotide arrays, and performed gene expression analyses using next-generation sequencing technologies in 22 human tumor samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs. Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs.