Cancer's Fingerprint

U-M study links new genes to prostate cancer

Like most killers, prostate cancer leaves fingerprints. Every malignant cell has a unique pattern of active genes and proteins that spells the difference between benign, localized or metastatic tumors. Hidden in this molecular profile are answers to questions doctors hear every day: Is surgery really necessary? Can I afford to wait? Will the cancer come back?

Until now, physicians have been unable to decode these fingerprints, which hold the key to understanding the relationship between gene expression and future prognosis for men with prostate cancer. But a new study from the University of Michigan Medical School, published in the August 23 issue of Nature, offers scientists their first look at the genetic and molecular profile of prostate cancer.

"Our study has important applications in the diagnosis, prognosis and treatment of pros-tate cancer," says Mark Rubin, M.D., a co-author of the Nature paper and an associate professor of pathology and urology in the U-M Medical School. "The ultimate goal is to help physicians determine which patients need immediate, aggressive treatment and which can be watched and treated more conservatively."

Rubin and colleagues at the U-M Comprehensive Cancer Center analyzed prostate tissue samples from 50 men and found nearly 200 genes or gene fragments in which activity profiles varied consistently, depending on whether the tissue was normal or malignant.

They then used DNA "chips" called microarrays to identify which genes were active in four types of tissue. These included normal prostate tissue from men with and without prostate cancer, tissue with benign changes, localized prostate cancer and aggressive, metastatic cancer. Tissue samples were obtained from the U-M Prostate Specialized Program of Research Excellence tumor bank, funded by the National Cancer Institute and directed by study co-author Kenneth Pienta, M.D., a professor of internal medicine and of surgery in the Medical School.

"Microarray technology allows us to look at thousands of genes in prostate cells simultaneously," says Arul Chinnaiyan, M.D., Ph.D., an assistant professor of pathology in the U-M Medical School, who directed the study. "This is important, because it is most likely that many genes are involved in the development and progression of prostate cancer-each controlling a different step in the process."

While some of the genes identified in the U-M study are well known to cancer researchers, many others have never before been associated with prostate cancer. Two of these new genes are hepsin and pim-1, which could turn out to be important new clinical biomarkers for prostate cancer, according to Rubin.

"This approach could give us many new diagnostic tests for prostate cancer within three to five years," says Rubin. Eventually, it could lead to a diagnostic kit physicians could use to determine the best treatment and prognosis for their patients with prostate cancer.

The research was supported by the National Cancer Institute's Specialized Program of Research Excellence in Prostate Cancer. The U-M has applied for a patent on prostate cancer gene expression profiles for future diagnostic and therapeutic use.

Other U-M scientists involved in the study include: Saravana M. Dhanasekaran, Ph.D., research fellow; Terrence R. Barrette, research associate; Debashis Ghosh, Ph.D., assistant professor of biostatistics in the U-M School of Public Health; Rajal Shah, M.D., assistant professor of pathology; Sooryanarayana Varambally, Ph.D., research fellow; and Kotoku Kurachi, Ph.D., professor of human genetics.

-Sally Pobojewski

Read the full story on the Web at:
www.cancer.med.umich.edu/news/relprostate.htm

See Arul Chinnaiyan's Web page at:
www.pathology.med.umich.edu/faculty/Chinnaiyan/biosketch.htm

See Mark Rubin's Web page at:
www.pathology.med.umich.edu/faculty/Rubin/biosketch.htm

For patient information on prostate cancer:
www.cancer.med.umich.edu/prostcan/prostcan.html