Fox Chase Cancer Center Researchers Look for "Silenced" Genes To Monitor Kidney Cancer Patients
ANAHEIM, CALIF. (April 18, 2005) -- Researchers at Fox Chase Cancer Center in Philadelphia say looking for genes that have been turned off by cancer cells may become a reliable and noninvasive way to detect and monitor cancer in the kidney. The data were presented today at the 96th Annual Meeting of the American Association for Cancer Research in Anaheim, Calif.
Tumor-suppressor genes are part of the body's natural defense against cancer. When inactivated-or "silenced"-they can no longer do their job, allowing cancer cells to grow. Cancer cells use a mechanism called hypermethylation to turn off the tumor-suppressor genes.
"Finding these 'silenced' genes is a good way to find cancer," said Essel A. Dulaimi, MD, a postdoctoral fellow at Fox Chase. "Abnormal patterns of methylation can be detected in many cancers, including kidney cancer," she added. Early diagnosis of kidney cancer can lead to earlier treatment with a curative outcome.
Dulaimi and fellow Fox Chase researchers used a molecular DNA-based test to determine the presence or absence of methylation in a particular gene. Called methylation-specific polymerase chain reaction (PCR), the test can find one methylated gene among 100 unmethylated alleles (genes at the same site on a specific chromosome).
"This specificity is enough to detect even a few cancer cells among healthy cells," explained molecular biologist Paul Cairns, PhD, lead researcher of the study.
In an earlier Fox Chase study with six methylated genes (Cancer Research, Dec. 15, 2003), Dulaimi, Cairns, urologic surgical oncologist Robert G. Uzzo, MD, and colleagues found an identical pattern of hypermethylation in both kidney tumors and urine collected before surgery. Forty-four of 50 urine samples (88 percent specificity) had a methylation pattern identical to the original tumor; all of the healthy patients showed no methylation (100 percent specificity).
"A gene that was postive for methylation in the urine was always positive in the matched tumor, " explained Cairns. "This is important because the DNA can be studied in the urine samples of patients who are being followed up after kidney surgery."
Thus, the methylation-specific test is a useful noninvasive tool. Until now, renal cancer could only be identified by a pathologist reviewing tumor tissue.
In the study presented today at AACR, the researchers tested samples from 25 patients aged 33 to 73 who had undergone surgery to remove cancerous tumors confined to the kidney. At follow-up after surgery, none of the 25 patients had clinical evidence of disease.
The researchers hypothesized that these patients-who earlier had methylated tumors but now had no clinical evidence of disease-would have a follow-up urine sample that would show no methylation. This would confirm that they were, in fact, clinically disease-free.
The results showed that two patients had the same methylated gene in their urine samples that was methylated in the tumor. The other 23 patients had unmethylated genes in their urine samples.
"This means that we can monitor the presence of cancer by checking DNA in the urine periodically and looking for hypermethylation," said Uzzo.
"Our studies have proved that looking for hypermethylation in specific tumor-suppressor genes is useful for finding kidney cancer," Cairns said. "Now, it can also be applied to clinical follow up for patients with renal cancer."
In addition to Dulaimi, Cairns and Uzzo, Fox Chase co-authors of the new study are postdoctoral associate Inmaculada Ibanez de Caceres, PhD; Richard E. Greenberg, MD, chief of urologic surgical oncology; and pathologist Tahseen I. Al-Saleem, MD, director of hematopathology and flow cytometry.
96th Annual Meeting of the American Association for Cancer Research
Poster Session: Molecular Markers in Diagnosis and Prognosis 3: Urologic Cancers
Exhibit Hall B-D, Anaheim Convention Center
Abstract #3152, Board #7:
Monitoring of Tumor-Suppressor Gene Methylation in Follow-Up Renal Cancer Patients
To be presented Monday, April 18, 2005, from 1 to 5 p.m. PT
Fox Chase Cancer Center, part of Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase also was among the first institutions to receive the National Cancer Institute’s prestigious comprehensive cancer center designation in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are routinely recognized in national rankings, and the Center’s nursing program has achieved Magnet status for excellence three consecutive times. Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research and oversees programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE (1-888-369-2427).