The universe of cancer mutations just got a whole lot bigger.

By analyzing the genomes of thousands of patients' tumors, a research team has discovered many new cancer genes, expanding the list of known genes tied to these cancers by 25 percent. Moreover, the study shows that many key cancer genes still remain to be discovered. The team says that creating a comprehensive catalog of cancer genes for scores of cancer types is feasible with as few as 100,000 patient samples.

But the take home message is that mutation remains unpredictable and the idea of 'curing' cancer has become more and more quaint. Still, therapy can be improved. 

Over the past 30 years, scientists had found evidence for about 135 genes that play causal roles in one or more of the 21 tumor types analyzed in the study. The new report not only confirms these genes, but, in one fell swoop, increases the catalog of cancer genes by one-quarter. It uncovers 33 genes with biological roles in cell death, cell growth, genome stability, immune evasion, as well as other processes.

The researchers estimate that they will need to analyze, on average, about 2,000 samples of each cancer type in order to catalog the vast majority of these mutations – our about 100,000 samples across roughly 50 tumor types. "Given that there are around 32 million people living with cancer worldwide, this is a very reasonable number to study," said co-author Gad Getz director of the Broad Institute's Cancer Genome Computational Analysis group.

The tumor types analyzed included those in which lots of mutations occur – such as melanoma and forms of lung cancer – and those that have a much lower frequency of mutations – such as rhabdoid and medulloblastoma, both childhood cancers.

In total, the researchers analyzed the genomes of nearly 5,000 cancer samples, comparing them with matched samples from normal tissue. Using methods that the group has pioneered over the last few years, they rediscovered nearly all previously known cancer driver genes for these types of cancer, validating their approach.

"One of the fundamental questions we need to ask ourselves is: Do we have a complete picture yet? Looking at cancer genomes tells us that the answer is no: there are more cancer genes out there to be discovered," said the paper's first author Mike Lawrence, a computational biologist at the Broad Institute. 

"We could tell that our current knowledge was incomplete because we discovered many new cancer genes," said Getz. "Moreover, we could tell that there are many genes still to be discovered by measuring how the number of gene discoveries grows as we increase the number of samples in our analysis. The curve is still going up!" 

The altered genes that the team has pinpointed will need to be followed up to determine which, if any, could be important targets for drug development. Initiatives at the Broad Institute like the Cancer Program's Target Accelerator intend to do just that. In the meantime, the new work offers a wider view of the cancer genomics universe, and new clues about what remains to be discovered if more samples are analyzed.