DNA analysis uncovers genetic errors behind 12 major cancers

Scientists at Washington University in St. Louis say it may someday be possible to perform a single test to screen for a wide range of cancer types.

Scientists led by Dr. Li Ding have analyzed the DNA of 3,281 tumors to find 127 repeatedly mutated genes that appear to drive the growth of a range of cancers. Robert Boston

Thanks to recent advances in genome sequencing that allow scientists to analyze DNA faster and more affordably than ever before, researchers at Washington University School of Medicine in St. Louis say they have found that many types of cancer are driven by the same genetic mutations.

The scientists have been able to analyze 3,281 tumors to find 127 genes that repeatedly mutate in such a way as to drive the development of tumors in the body.

Previous genome studies have tended to home in on specific tumor types, but the work out of St. Louis, which appears this week in the journal Nature, is among the first to look at a wide range of what are sometimes seemingly unrelated tumor types. In fact, the thousands of tumors they analyzed included 12 major cancers: of the breast, uterus, bladder, kidney, ovary, lung, brain, blood, head and neck, and colon and rectum.

"This is just the beginning," senior author Li Ding of the university's Genome Institute said in a school news release of her team's findings. "Many oncologists and scientists have wondered whether it's possible to come up with a complete list of cancer genes responsible for all human cancers. I think we're getting closer to that."

In fact, the researchers say they envision a future where it's possible to perform a single test to survey all 127 of these identified genetic errors as part of a standard diagnostic workup for most cancers. Such a test could, in turn, not only identify unique genetic signatures of tumors but open the door for highly personalized cancer treatments as well.

While the researchers found common links between genes in different cancers (for instance, one gene mutated in 25 percent of leukemia cases was also found in seven other tumor types), they also found mutations that are particular to one.

To add to the complexity, some of the 127 genetic errors occur frequently in certain cancers, while some appear rarely in others, but all are being considered an important part of the growth of the cancers. The researchers did find, however, that most tumors had only two to six genetic mutations. Ding said that because cells are constantly accumulating new mutations over time, the finding that only a couple of mutations are key to turning a healthy cell into a cancerous one could help explain why cancer is so common.

The DNA analysis also helped the researchers identify genes that correlate strongly with not only cancer types but actual prognosis. TP53, for instance, was found more than any other across the different tumor types -- in 42 percent of the samples -- and is particularly bad news in cancers of the kidney, head and neck, and acute myeloid leukemia. BAP1, too, was often linked with poor prognoses, especially in kidney and uterine cancers.

On the other end of the spectrum, mutations in the gene BRCA2, which drives breast cancer, correlated with improved survival in ovarian cancer, while mutations in IDH1 were linked to better outcomes in patients with very aggressive brain tumors, among other cancer types.

In spite of the many exciting findings, the work has, as Ding said, just begun. The team, which gets its funding from the National Cancer Institute, the National Human Genome Research Institute, and the National Science Foundation, hopes to continue to beef up its list of cancer genes in the quest to further fine-tune cancer diagnosis and treatment.

 

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