Researchers Develop New Method of Screening Tumors

Researchers at the Harvard-affiliated Dana-Farber Cancer Institute have developed a new method of screening tumors for key cancer-related gene abnormalities. The finding, published in an advanced online edition of the scientific journal Nature Genetics, is a major step towards the development of personalized cancer treatments.

Different patterns of gene expression are associated with different types of cancers, but identifying the various mutations that contribute to each kind of cancer is a laborious and costly process.

“Millions and millions of dollars are spent just to recognize mutations in a few cancers when ideally, you would want to know that information for the whole spectrum of cancers,” said the study’s senior author, Levi A. Garraway, an instructor in medicine at Dana-Farber.

A second challenge, according to Garraway, is the “bottleneck” that occurs when trying to put our expanding knowledge of how genetic mutations cause cancer into practice in the clinic.

“Hundreds of these mutations are now known, but the challenge is how we extract relevant information from patients who walk into the clinic without having to sequence all of their genes,” said Garraway.

The study presents a streamlined way of detecting mutations in key oncogenes, or genes that promote cancer growth. By adapting a common scientific method called high-throughput genotyping to target specific sequences in oncogenes susceptible to mutations, Garraway obtained accurate mutation profiles of 17 oncogenes.

A profile of an individual’s gene expression pattern can provide doctors with important details, including disease prognosis and how a patient may respond to certain drugs. According to Garraway, few diagnostic tests exist currently that can provide patients with mutation information for multiple genes.

“Until recently we have had to use direct sequencing to find specific mutations in tumors,” wrote William C. Hahn, associate professor of medicine at Harvard Medical School, in an e-mail. “While this can be done, it is a bit of an involved process and can be quite expensive.”

According to Garraway, the average cost of profiling each sample in his experiment was under $100.

Although the technique has yet to be tested in the clinic, Garraway believes his results have clinical potential as a rapid, cost-effective and accurate means of diagnosing cancer. He said that his discoveries point towards a day when tumor profiles will allow doctors to select the best cancer drugs for their patients.

“When fully implemented clinically this approach will usher in an age of truly personalized cancer treatment, based on an exact understanding of the genetic changes and vulnerabilities present in an individual’s cancer,” wrote Myles Brown, chief of the Division of Molecular and Cellular Oncology at Dana-Farber, in an e-mail. “This is sure to lead to both more effective and less toxic treatments and improved outcomes for our patients.”

—Staff writer Xianlin Li can be reached at li3@fas.harvard.edu.