Genetic Markers Responsible for Recurrence

In the study Malcolm Brock, M.D., associate professor of surgery at Johns Hopkins and his team report how they combed through more than 700 surgical samples from 167 early stage, non-small cell lung cancer patients searching for specific methylation patterns linked to the disease. Tumor and lymph node tissue from 51 patients whose cancers recurred within 40 months were compared with samples from the remaining 116 patients whose cancers did not recur.

The scientists tested all the samples for methylation on seven genes linked to the development of lung cancer. Four of them - p16, H-cadherin, APC and RASSF1A - showed the highest amounts of methylation in patients whose cancers recurred. For many of the genes, the study revealed a twofold difference in methyl marks between recurrent cancers and those that did not return.

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.; Source: Johns Hopkins Medicine