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

Researchers at the Johns Hopkins Kimmel Cancer Center have uncovered clearly recognizable genetic alterations in tumors and tissue removed from patients with early-stage lung cancers that look like good predictors of which of these cancers are more likely to recur.

The discovery, they say, could change the approach to treating even the smallest lung cancers - the size of a pea - which are known to recur within five years in 30 to 40 percent of patients.

“This is DNA forensics for cancer,” says Malcolm Brock, M.D., associate professor of surgery at Johns Hopkins. “While there may be no trace of cancer that we can spot after surgery with a microscope, the DNA evidence from these tumors may have been left at the scene, especially in lymph nodes.”

The particular molecular flags the team identified are chemicals known as methyl groups that latch on to the DNA ladder structure of a gene. Methylation is a commonly known phenomenon in the formation and development of cancers because they serve as signals to cells to switch certain genes on or off. Disruption in these signals may create a cascade of abnormal proteins that lead to cancer or its recurrence.

In the study published in the March 13 issue of the New England Journal of Medicine, Brock 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.

“The DNA evidence we see for many of the recurring cases suggests it may be wise if our work is confirmed to reclassify such cancers as advanced disease instead of early stage,” says Brock.