Methylation of RAS association domain family protein 1A as a biomarker of lung cancer

BACKGROUND. Promoter hypermethylation is an important mechanism for silencing tumor-suppressor genes in cancer and a promising tool for development of molecular biomarkers. This study aimed to determine the prevalence of RAS association domain family protein 1A (RASSF1A) promoter hypermethylation in bronchial aspirates of patients with suspected lung cancer and to test whether this type of methylation assay could be used as a diagnostic adjunct to conventional cytology. METHODS. Two hundred three bronchial aspirates from patients with suspected lung cancer were analyzed for RASSF1A hypermethylation by using a sensitive quantitative methylation-specific polymerase chain reaction (QMSP). RESULTS. RASSF1A hypermethylation was found in 88% (35 of 40), 28% (31 of 111), and 100% (6 of 6) of bronchial aspirates collected from patients diagnosed with small cell lung cancer, nonsmall cell lung cancer, and combined small cell lung cancer, respectively. No hypermethylation was detected in patients diagnosed with nonneoplastic lung disease (0 of 46). Depending on histologic subtype, up to 82% of cases presenting with a negative histology showed a positive methylation assay. CONCLUSIONS. The QMSP analysis of RASSF1A hypermethylation enabled a highly specific distinction between patients diagnosed with lung cancer and those with nonneoplastic lung disease. These results suggested that a QMSP assay is a promising molecular tool for diagnosis of primary lung cancer.