Genetic profiling could predict cancer

Researchers at Duke, using new genetic profiling analysis, have developed a method of classifying breast cancers.

Currently, pathologists rely on visual examination of a tumor to determine its potential malignancy.

"Breast cancer tumor analysis is done on visual information, but it is very limited," said senior author Dr. Joseph Nevins, chair of the genetics department and interim director of the Center for Genome Technology. "Subtle, slight differences in one's genes may make two tumors look the same, but they could behave very differently. This technique goes beyond the standard practice."

Thousands of genes are fixed on a postage stamp-sized chip, called a DNA microarray, to help researchers identify the exact location of a gene in the entire genome. Nevins and his team analyzed 100 genes from 49 tumor samples, and found that breast cancer could be distinguished by two critical factors: estrogen receptor status and lymph node status.

Tumors expressing estrogen receptors are more likely to spread aggressively, while tumors that have spread to lymph nodes constitute the most important indicator of cancer metastasis. By looking at microarrays, researchers were able to find patterns that were signature representations of these different gene expressions.

"This tool takes advantage of a technology [created] from developments in genomics research," Nevins said. "This enables us to measure activity of gene expression on a large scale, and there is power in getting a global view."

The findings were published in the Sept. 25 issue of The Proceedings of the National Academy of Sciences.

"I think as a prognostic tool, genetic profiling will be helpful to add information on top of what we already know, and to predict who should get what drugs," said Dr. Charles Perou, assistant professor of genetics at the University of North Carolina at Chapel Hill. "This sort of analysis will help us make better predictions and better define the biology of a person's tumor."

Nevins also points to other benefits of this diagnostic approach. For example, if it is shown to be clinically effective, it could eliminate the need for doing extensive and risky surgery to remove lymph nodes and reduce the discomfort of patients.

In addition to helping researchers identify tumors that show characteristics of metastasis, Nevins predicts this tool will be used to define more clearly who will respond to more aggressive treatment. Furthermore, it may lead to developments in novel drugs and treatment approaches that are more specific in treating cancer.

"The hope is that this information will help us understand the root differences in [estrogen receptor and lymph node states], and develop drugs that take advantage of these differences," Nevins said. "This [prognostic tool] will have a huge impact fairly soon. I would be very surprised if this test analysis doesn't appear in clinics [in the near future]."

Perou agreed, stressing how this method differs from current diagnostic procedures. "This new genomic technology is being used to address the oldest question in the book, which is, OWhat makes tumors different?'" he said. "This tool is allowing us to detect differences that we've never seen before--differences that clearly have very important biological and clinical diagnostic implications."

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