Profiles in cancer. (Molecular Biology).

Historically, pathologists have struggled to distinguish many of the 50-plus sarcoma subtypes, which often look similar under a microscope. Misidentification could hamper treatment--an oncologist who doesn't realize a tumor is aggressive, for example, might treat it too conservatively, allowing it to spread. Now, however, genetic profiling of several of the most common sarcomas--similar to the DNA fingerprinting used to identify criminals--may enable pathologists to accurately diagnose most soft-tissue sarcomas.

Soft-tissue sarcomas are rare; about 8,700 new cases are diagnosed each year. Soft-tissue sarcomas rank among the deadliest cancers, with a five-year survival rate of about 50%. Studies have implicated Agent Orange and other dioxin exposures. Some cases have been associated with therapeutic radiation, others with workplace exposure to vinyl chloride (used, for example, to produce plastics). Most sarcomas, however, have no known cause.

"Because sarcomas are rare, most pathologists don't see many of them," says Matt van de Rijn, an associate professor of pathology at Stanford University School of Medicine. "This [technology] will increase our ability to diagnose sarcomas." Van de Rijn and his colleagues published a study of sarcoma profiling in the 13 April 2002 issue of The Lancet. Other researchers are conducting similar sarcoma studies at Memorial Sloan-Kettering Cancer Center, the University of Minnesota, the University of Utah, and several institutions in Europe. At the 38th annual meeting of the American Society of Clinical Oncology in May 2002, the Sloan-Kettering team presented research in which they developed DNA expression profiles that can be used to accurately diagnose nine soft-tissue sarcoma subtypes, representing approximately 70% of these cancers.

To develop such profiles, researchers use a gene-expression microarray, or "gene chip." The chip contains thousands of known gene samples printed onto a quartz wafer in tiny dots. When a gene in a study cell matches one on the chip, it binds tightly, like two pieces of a puzzle. The cellular material causes the matched gene dot to light up. A computer than analyzes the pattern of luminescent genes that make up the cell's profile.

The profiling technique can potentially improve the prognosis for countess patients with more common forms of cancer. "This is a very general technique that will have ramifications for all types of cancer, including the more common ones such as lung, breast, colon, and prostate," says Robert Maki, a medical oncologist and investigator in the Sloan-Kettering work. "All the common cancers are being investigated." Scientists from the National Human Genome Research Institute and Lund University in Sweden reported in the 1 June 2001 issue of Nature Medicine that they used genetic profiling to distinguish four childhood cancers that look similar under a microscope: neuroblastoma, rhabdomyosarcoma, non-Hodgkin lymphoma (Burkitt lymphoma), and Ewing sarcoma.

Profiling may eventually help oncologists select the best drugs for treatment. For example, the gene ERCC1 is associated with resistance to cisplatin, a key drug used in treating ovarian cancer. Oncologists who know that a patient expresses the ERCC1 gene would choose other drugs. Pharmaceutical researchers also can use this information in drug development to design new chemotherapy drugs that disable drug-resistant genes or target susceptible genes. "If we can identify [genetic] targets," says Maki, "we may be able to develop drugs that attack those targets."