Scientists identified 18 new genes responsible for driving glioblastoma multiforme, the most common and most aggressive form of brain cancer in adults. The team of scientists from Columbia used a combination of high throughput DNA sequencing and a new method of statistical analysis to generate a short list of driver candidates. The massive study of nearly 140 brain tumours sequenced the DNA and RNA of every gene in the tumours to identify all the mutations in each tumour.
A statistical algorithm was then used to identify the mutations most likely to be driver mutations. The algorithm differs from other techniques to distinguish drivers from other mutations in that it considers not only how often the gene is mutated in different tumours, but also the manner in which it is mutated.
The analysis identified 15 driver genes that had been previously identified in other studies - confirming the accuracy of the technique - and 18 new driver genes that had never been implicated in glioblastoma.
Significantly, some of the most important candidates among the 18 new genes, such as LZTR1 and delta catenin, were confirmed to be driver genes in laboratory studies involving cancer stem cells taken from human tumours and examined in culture, as well as after they had been implanted into mice.
The study found that half of about 15 percent of patients have tumours driven by a fusion between the gene EGFR and one of several other genes.
The fusion makes EGFR - a growth factor already implicated in cancer - hyperactive; hyperactive EGFR drives tumour growth in these glioblastomas.