DNA detectives find genetic markers for lung cancers most likely to recur

Brock and his colleagues also found that cancers returned even more swiftly than average for 11 patients who had higher than normal methylation in a deadly combination of two genes known as p16 and H-cadherin located in both tumor tissue and a lymph node distant from the original tumor area. Eight of the 11 patients with this methylation pattern had cancers that returned within a year. By 30 months, the remaining three patients’ cancer had also recurred.

The investigators did analyze the results to quantify the odds that a particular patient’s cancer would recur, noting a five to 25-fold increase in risk depending on the particular methylation pattern. They caution that while some of the gene markers lack statistical significance because of small sample size, odds predictions are valid for the two most promising genes - p16 and H-cadherin.

Kimmel Cancer Center medical oncologist James Herman, M.D. says if these results are confirmed, it may lead doctors to consider treating high-risk patients more aggressively with chemotherapy after surgery. He also believes that therapies which target these gene patterns by stripping off methyl groups hold promise as well. “These marks of aggressive disease also are themselves targets for therapy.”

Additional studies of the methyl markers are under way on lung cancer patients currently being treated at Johns Hopkins.

Cure rates for lung cancer are far lower than for other common cancers such as breast or prostate. Lung cancer is the deadliest cancer and second most common in the United States.

Funding for the study was provided by the National Cancer Institute’s Specialized Program of Research Excellence (SPORE), the Commonwealth Foundation for Cancer Research, the Hodson Trust, and OncoMethylome Sciences.

Additional research participants include Craig M. Hooker, Emi Ota-Machida, Yu Han, Mingzhou Guo, Stephen Ames, Sabine Glöckner, Steven Piantadosi, Edward Gabrielson, Genevieve Pridham, Kristin Pelosky, Stephen C. Yang and Stephen B. Baylin from Johns Hopkins; and Steven A. Belinsky from the Lovelace Respiratory Research Institute.

Herman and Baylin are consultants to and receive research support from OncoMethylome Sciences. Under licensing agreement between the Johns Hopkins University and OncoMethylome, methylation specific PCR was licensed to OncoMethylome and they are entitled to a share of the royalties received by the University from sales of the licensed technology. Brock receives research support from OncoMethylome Sciences.

On the Web:
www.hopkinskimmelcancercenter.org