Taking Cancer’s Fingerprint: Rapid genetic profiling for personalized therapy

A new, faster way to identify cancer-causing mutations in the DNA of tumor cells may pave the way for the next generation of custom-tailored cancer therapies.

The cells of each person’s cancer show a particular pattern of genetic changes, and those changes vary even among people with the same kind of cancer. Therapies that have been custom tailored for specific cancer mutations can have increased effectiveness and fewer harmful side effects than do conventional cancer drugs that attack tumors more generically.

The use of tailored therapies requires genetic screening of tumors. By making that screening more practical, the DNA-profiling technique may expand the use of targeted approaches. Doctors currently screen patients’ tumors for mutations only occasionally, in part because current techniques can sequence just one gene at a time and cost hundreds of dollars. The new method can scan for hundreds of cancer-related mutations simultaneously for roughly the same cost.

“If you’re really thinking about being targeted in your therapy, you don’t want to know about just one or two genes. You want to be able to screen lots of genes for hundreds of specific mutations to know which targeted therapy to use,” says Levi Garraway, who helped develop the technique at the Dana-Farber Cancer Institute in Boston.

Garraway and his team took an existing approach for detecting specific variations in genes and used it to look for mutations known to be associated with cancer. The scientists placed copies of a tumor’s DNA into tiny pits arranged in a grid on a sample plate. Then, they added to each pit different chemicals that respond to particular mutations. A machine automatically measured that response for all the pits.

“The big difference with [this technique] is the breadth of the sensitivity,” Garraway says. The researchers scanned for 238 specific mutations in 17 cancer-related genes, they report in the March Nature Genetics. When they tested their technique on 1,000 human-tumor samples, they found one or more of these mutations in about 30 percent of the samples—the same percentage achieved in previous research using the slower, more expensive gene sequencing.

“Theirs is an important step,” comments Stephen J. Chanock of the National Cancer Institute in Bethesda, Md. The wide variety of mutations that the group found underscores the vast and poorly understood complexity of tumor genetics. “Scope and size are everything here,” Chanock says.

Fewer than a dozen targeted cancer drugs have been approved for clinical use, but many others are under development. Garraway says that he expects the number of targeted therapies available to grow rapidly in the next few years.

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