High-throughput mutation profiling for cancer

13 February 2007

The latest contribution to the field of genetic profiling of human cancers is a new paper in the advanced online edition of Nature Genetics. There have been many papers concerned with the application of microarray analysis to identify patterns of gene expression associated with different molecular subtypes of cancer, and the development of prognostic indicators based on the expression of key sets of genes. The new work by a team of scientists based at the Dana-Farber Cancer Institute in the US takes a slightly different approach by setting out a form of genetic tumour screening for the presence of key mutations that could direct the development of novel, genetically targeted therapeutics.

Overall, there are hundreds of potential mutations in multiple oncogenes that may direct the formation and progression of cancers. However, the researchers theorized that by selecting genetic assays for the most common mutations in major oncogenes, it should be possible to identify a large proportion of oncogenic mutations with a limited number of assays. They therefore employed high-throughput genotyping processes to detect the presence of 238 previously characterized oncogenic mutations (in seventeen key oncogenes) in a total of 1000 human tumour samples [Thomas RK et al. (2007) Nat Genet. Feb 11; Epub ahead of print]. The oncogenes selected for analysis were all of high prevalence, or had established associations with clinical features or therapeutic responses.

Mutations were identified in around a third of the samples, and included novel mutations as well as sets of different mutations that tended to occur together. New insights into the genetic nature of different tumours may aid the development of new therapeutics targeted to these unique genetic features. The total cost of mutation profiling for each sample in the study was reported to be in the region of $50-$100 (approximately £25-£50). The research team proposes that the technique has clinical potential as a rapid, cost-effective and accurate means of correctly diagnosing cancer; in the future, by determining the genetic tumour profile, it may also be possible to select the most appropriate therapeutic. Lead author Dr Levi Garraway said: "It is a step toward the day when cancer patients will routinely have their tumors scanned for specific mutations, and treatment will be based on the cancer's particular genetic profile" (see press release).

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