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Identification of Novel Lung Genes in Bronchial Epithelium by Serial Analysis of Gene Expression

Cancer Genetics and Developmental Biology, Department of Cancer Imaging, Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre; and Computer Science, University of British Columbia, Vancouver, British Columbia; and Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Ontario, Canada

Correspondence and requests for reprints should be addressed to Kim Lonergan, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3 Canada. E-mail: klonergan{at}bccrc.ca

A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases, including cancer. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based on a vast dataset of nearly two million sequence tags from 21 serial analysis of gene expression (SAGE) libraries from individuals with a history of smoking. Our analysis suggests that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. Moreover, our analysis has identified novel bronchial-enriched genes such as MS4A8B, and has demonstrated the use of SAGE for the discovery of novel transcript variants. Significantly, gene expression associated with ciliogenesis is evident in bronchial epithelium, and includes the expression of transcripts specifying axonemal proteins DNAI2, SPAG6, ASP, and FOXJ1 transcription factor. Moreover, expression of potential regulators of ciliogenesis such as MDAC1, NYD-SP29, ARMC3, and ARMC4 were also identified. 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, and constitutes one of the largest human SAGE studies reported to date.

Key Words: bronchial epithelial • ciliogenesis • expression profile • lung parenchyma • SAGE

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