ABSTRACT: 2 normal lung parenchyma SAGE libraries, generated from 2 pools of 4 individuals each Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: lung parenchyma