Dr. Richard Alexander, a surgical oncologist at the University of Maryland who was not involved in the study, called the Hopkins discoveries "a big breakthrough," but he counseled patience.
"The initial assessment is that this is huge," he said. "But the reality is ... it does take time to understand how to use it." Cancer patients should not expect new therapies and cures to emerge quickly from the research, he said.
The Hopkins team tackled brain and pancreatic cancers because they are so lethal. An estimated 38,000 Americans will develop pancreatic cancer this year. Fewer than 5 percent will be alive five years after diagnosis. Another 20,000 people will develop brain cancers, with a similarly grim survival rate.
The Hopkins team began with tumor cell samples from 22 patients with brain cancers called glioblastoma multiforme, and from 24 patients with pancreatic cancer.
They sequenced all 20,661 genes that guide the production of proteins, and compared them with genome data from healthy brain and pancreatic tissue.
They discovered 83 genes in the pancreatic tumors and 42 in the glioblastoma cells whose chemical sequences had mutated in some way, making them prime suspects in the uncontrolled cell reproduction that defines cancer.
Gene defects related to cancer have been discovered before. Dr. Bert Vogelstein, a professor of oncology at Hopkins and a co-author of the Science study, said nearly all cancer drugs developed in the last decade were designed to silence a particular defective gene, or cut off its expression in tumors, thereby killing the cancer. And some have been effective.
But the study found that the damaged genes in these tumors don't work in isolation from each other. Instead, constellations of altered genes appear to combine their output, functioning together in patterns or sequences called "pathways" that allow uncontrolled growth to continue.
"A simpler picture emerges," Kinzler said. "Often, what appear to be mutations in disparate genes were found to be working in concert to achieve similar effects."
For example, the researchers identified a core set of 12 altered genetic pathways that affected two-thirds of the pancreatic tumors they analyzed.
By designing therapies that attack and interrupt such "core" pathways, rather than the dozens of individual genes that play a role in them, the challenge to cancer fighters would be greatly simplified. It could be likened to stopping traffic by raising a drawbridge rather than disabling a thousand cars.
