DETECTION OF ONCOGENE MUTATIONS IN SPUTUM PRECEDES DIAGNOSIS OF LUNG-CANCER

The Johns Hopkins Lung Project developed an archive of sputum specimen s during a randomized trial of lung cancer screening (1974-1982). We i dentified 15 patients from that trial who later developed adenocarcino ma of the lung. The primary lung carcinomas from 10 of these 15 patien ts contained either a ras or a p53 gene mutation. Using a polymerase c hain reaction-based assay. stored sputum samples obtained prior to cli nical diagnosis were examined for the presence of these same oncogene mutations. In 8 of 10 patients, the identical mutation identified in t he primary tumor was also detected in at least one sputum sample. The earliest detection of a clonal population of cancer cells in sputum wa s in a sample obtained more than 1 year prior to clinical diagnosis. T hese results provide the basis of a novel approach for detection of lu ng cancer based on the evolving molecular genetics of this disease.