Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer

We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25, TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection, this eight-locus panel showed 95.6% sensitivity and specificity.We have identified 22 DNA methylation markers for squamous cell lung cancer, several of which have not previously been reported to be methylated in any type of human cancer. The top eight markers show great promise as a sensitive and specific DNA methylation marker panel for squamous cell lung cancer.Cancer is responsible for one in four deaths in the US, making it the second most common cause of death [1]. Lung cancer is the leading cancer killer in men and women.Over 160,000 Americans will die of this disease in 2007. In men, lung cancer accounts for 31% of cancer deaths, killing more men than leukemia and prostate, colorectal, and pancreatic cancer combined. In women, lung cancer accounts for 27% of all cancer deaths, taking as many lives as breast and colorectal cancer combined [1]. The overall five-year survival rate of lung cancer patients is 15%, significantly lower than that of patients with prostate cancer (99.9%), breast cancer (88.5%) or colon cancer (64.1%) [1]. This rate increases dramatically to greater than 50% when lung cancer is diagnosed at an early stage. However, only 14–16% of cases are detected early [1].In contrast to breast, colon, and prostate cancer, no routine screening method for early detection of lung cancer exists. Methods based on imaging (chest X-ray, low dose spiral computed tomography (LDSCT), autofluorescence bronchoscopy (AFB)), and sputum cytology have been tested, however, none have proven ideal. Screening via chest X-ray is not sufficiently sensitive [2], and trials demonstrated that its use in high risk populations showed no decrease in mortality [3].