"When it became clear in the 1990s that novel tumour suppressor genes could be discovered by looking at genome deletions, many hands were put to the pump," explains Dr Andy Futreal, co-leader of the Cancer Genome Project. "But it became clear that it wasn't quite that simple. New tumour suppressor genes just weren't that easy to find, despite the presence of many deletions. We now have some insight as to why: many of the regions being studied were actually fragile sites."
Because the researchers were looking in cancer cell lines for genes that have been deleted they also uncovered genes that are simply not required for cells to grow, at least in the artificial environment of the laboratory test tube. In aggregate, over the almost 750 cancer cell lines used in the study, one in nine genes was deleted and therefore not mandatory for the cells to live and grow.
Previous studies showed that one in 100 genes on the X chromosome can be inactivated without apparent effect on the well being of the whole person, while similar work across the genome suggested that one in 50 genes can be inactivated in apparently healthy people. Thus, predictably enough, cancers seem to be more tolerant than healthy people and can lose a much greater proportion of their genes without being impaired.
For cancer research, developing novel methods to discern the driver mutations remains a crucial goal.
"This is one step in building a suite of tools to draw out the important suspects in cancer genetics," continues Professor Stratton, "tools that will make the most of the massive efforts that lie ahead from organizations such as the International Cancer Genome Consortium, which will sequence as many as 500 samples from each of 50 cancer types over the next few years.
"Our results also illuminate novel findings that emerge from genome wide research, light that is shone on other corners of genome biology. While we mustn't overstate this - these are cancer cells growing in test tubes - it is fascinating to see the catalogue of genes that are not required for basic survival."
Source: Wellcome Trust Sanger Institute