Scientists compile cancer gene map
genome of the fruit fly (Drospohila melanogaster) for genes
that could play a role in cancer.
The researchers hope a similar technique can also be used to identify cancer genes in the human genome, and provide new targets for drug discovery.
Dr Michael Boutros of the Deutsches Krebsforschungszentrum (German Cancer Research Center and colleagues used Drosophila blood cells to analyse the function of almost 20,000 different genes.
In the process, they identified more than 400 genes that are needed for cell proliferation and survival - key criteria for tumour development. Among these were a number genes whose relatives in the human genome are known to be involved in cancer. For example, mutations in the AML1 gene have been implicated in acute myeloid leukemia.
While screening the Drosophila genome, the researchers discovered that the fruit fly counterpart of AML1 has a function in cell survival, providing an immediate validation of the technique and supporting the hypothesis that a mutated AML1 gene prevents the cell from activating its natural program of self-destruction.
Boutros et al used a gene silencing method called RNA interference (RNAi) to selectively analyse the functions of individual genes.
They first selected from a database the sequences of all the genes to be investigated, and made RNAi probes that could be used to deactivate each one. The RNAi sequences were then applied to cells in order to silence their natural gene counterparts. If the cells died or stop dividing, then the investigators knew that the respective gene must play an important role in cell survival or proliferation.
The method does not yet work genome-wide in human cells, so researchers are using model organisms such as the fruit fly to provide clues to the corresponding sequences in humans.
The more insights scientists get into the molecular basis of cancer, the more apparent it becomes that it is rarely based on changes in a few individual genes. Rather, several small steps together cause the complex interactions of genes and gene products to fail, ultimately leading to the transformation of a cell.
According to Boutros, the next step after deciphering the genome is a systematic investigation of gene functions and interactions. His group are also working on methods to use RNAi screening in human cells. This might allow, for example, to systematically determine the function of genes in tumour cells and compare them in different types of cancer.The research is published in the journal Science (6 February).
