January 26, 2014
Landmark Study Expands Knowledge Of Cancer Genomics
April Flowers for redOrbit.com - Your Universe Online
A research team led by the Broad Institute has released the findings of a landmark study across many cancer types. The findings, published in Nature, reveal that the universe of cancer mutations is much bigger than scientists previously thought.
For their study, the team analyzed the genomes of thousands of patients' tumors, which allowed them to expand the list of known genes tied to these cancers by 25 percent. The study also demonstrated that many key cancer genes still remain to be discovered. The findings also lay a critical foundation for future cancer drug development, as well as showing that it is possible to create a comprehensive catalog of cancer genes for untold numbers of cancer types with as few as 100,000 patient samples.
"For the first time, we know what it will take to draw the complete genomic picture of human cancer," said Broad Institute founding director Eric Lander. "That's tremendously exciting, because the knowledge of genes and their pathways will highlight new, potential drug targets and help lead the way to effective combination therapy."
For the last three decades, researchers have found evidence for about 135 genes that play causal roles in one or more of the 21 tumor types that were analyzed in this study. These genes are confirmed by the new results, however, the results don't stop there. They also increased the catalog of cancer genes by one-quarter, uncovering 33 genes with biological roles in cell death, cell growth, genome stability, immune evasion, and other processes.
"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 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 Gad Getz director of the Broad Institute's Cancer Genome Computational Analysis group and a Broad associate member. Getz is also the director of the Bioinformatics Program at Massachusetts General Hospital Cancer Center and the department of pathology. "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!"
To catalog the vast majority of these mutations, the researchers estimate they will need to analyze roughly 2,000 samples of each cancer type. This averages out to about 10,000 samples across approximately 50 tumor types. "Given that there are around 32 million people living with cancer worldwide, this is a very reasonable number to study," said Getz.
The team analyzed tumor types 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) for the current study.
Nearly 5,000 cancer sample genomes were analyzed, in total. The team compared them with matched samples from normal tissue. To validate their approach, the team used methods pioneered by the group over the last few years to rediscover nearly all previously known cancer driver genes for these types of cancer.
Follow up will be needed to determine which, if any, of the altered genes pinpointed by the team could be important targets for drug development. The Broad Institute has initiatives such as the Cancer Program's Target Accelerator aimed at doing just that. Until then, the new findings offer a wider view of the cancer genomics universe, and tantalizing clues about what remains to be discovered if more samples are analyzed.