Lung cancer is the leading cause of death among all cancers and it has the highest cancer death rate in the United States. To identify molecular markers, we have used a differential display method to analyze total RNAs isolated from two human lung tumor cell lines, NCI H209 and H69, and a cell line CCD 8Lu, derived from normal human tissue. We have identified a cDNA clone 6-6-1 which is expressed at a higher level in both small cell lung carcinoma (SCLC) and non small cell lung carcinoma (Non SCLC) cells compared to cell lines derived from normal lung tissue. In matched tumor and normal lung tissues, gene 6-6-1 is expressed at higher levels in tumor than in normal tissue. Gene 6-6-1 is expressed at low levels in most human tissues except for kidney, small intestine and prostate, where it is expressed at higher levels. DNA sequence analysis of cDNA clones from normal lung and kidney, and from lung tumor cells revealed that a small deletion and transversion have occurred in tumor cells (in some cDNA clones) but not in normal cells. Gene 6-6-1 encodes a protein of relative molecular size of 32 kDa. 6-6-1 gene is mutated and deleted in H69 lung tumor cell line; both lead to an introduction of TAG termination codon and therefore cannot code for 32 kDa protein. Isolation of full-length normal lung cDNA clone, chromosome localization of 6-6-1 gene, relationship between the mutation and function of the protein and diagnostic potentials of mutations in lung and other types of cancer are under investigation.
