Researchers Find Mutation ‘Hotspots’ That Are Linked to Cancer

Researchers say they’ve identified clusters of genetic mutations in proteins that can give rise to cancer, a discovery that may help them zero in on new treatments.

Those mutation “hotspots” occur among families of proteins produced by genes in the body’s cells. By sifting through data from nearly 6,000 cancer patients, researchers at the University of Maryland say they found thousands of mutations that occur among those proteins.

They identified hundreds of protein families they dubbed “oncodomains,” suggesting the mutations that produced them play a role in the disease. The findings were published this week in the journal PLOS Computational Biology.

"Maybe only two patients have a mutation in a particular protein," Maricel Kann, the paper’s senior author, said in a statement accompanying the study. “But when you realize it is in exactly the same position within the domain as mutations in other proteins in cancer patients, you realize it's important to investigate those two mutations."

The research focused on what are known as somatic mutations -- a genetic change that occurs during a person's lifetime, rather than something passed down from their parents. Those mutations can cause the resulting cells to reproduce wildly, leading to cancer.

Cancer is the second-biggest cause of death in the United States, claiming nearly 600,000 lives a year. In the battle against the disease, scientists increasingly are honing in on how those mutations arise and using new tools in an attempt to correct them. Genetic testing also has helped patients find hereditary risks that their families didn’t know about before.

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The Maryland study looked at protein families where signs of a specific cancer type occurred more frequently than random chance would predict. They identified more than 850 they considered oncodomains. Those contained nearly 6,000 mutations that were associated with 20 different types of cancer, including skin, kidney, and neck cancers, the researchers reported.

“Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer,” the paper concludes. Analyzing cancer through these mutation clusters could become an important tool for analyzing the genetic makeup of tumors, which could give scientists a break in looking for ways to attack those cancers.

"Because the domains are the same across so many proteins, it is possible that a single treatment could tackle cancers caused by a broad spectrum of mutated proteins,” Kann said.

The project was funded by the National Science Foundation and the National Institutes of Health.

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