We used the serial analysis of gene expression (SAGE) method to systematically analyze transcripts present in non-small cell lung cancer. Over 226,000 SAGE tags were sequence analyzed from two independent primary lung cancers and two normal human bronchial/tracheal epithelial cell cultures. A total of 226,000 SAGE tags were sequence identified, representing 43,254 unique transcripts. Comparison of the tags present in the tumor with those identified in the normal tissue revealed 175 transcript tags that were overrepresented in the normal tissue and 142 tags that were overexpressed in the tumor by 10-fold or more. Northern hybridization was performed on 15 of the most abundantly expressed tags identified in the tumors. These tags were derived from either a known gene or a matched expressed sequence tag clone. The transcripts for 3 of the 15 genes, PGP 9.5, B-myb, and human mutT, were abundantly expressed in primary lung cancers (10 of 18, 15 of 18, and 6 of 12 tumors, respectively). In contrast, the presence of PGP9.5 and B-myb was much less frequent in primary tumors derived from other tissue origins. These results suggest that at least a portion of the transcripts identified by SAGE are frequently associated with lung cancer, and that their overexpression may contribute to lung tumorigenesis. The identification and further characterization of genes generated by SAGE should provide potential new targets for the diagnosis, prognosis, and therapy of lung cancer.

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Supported in part by grants from NIH Lung SPORE CA58184, Oncology CORE CA6973, and an award from the V-Foundation for Cancer Research (to J. J.).

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