We have surveyed more than 374,000 SAGE tags representing 66,502 unique transcripts from nine different lung tissue libraries. These libraries included two of each from normal small or large airway epithelial cell cultures, two of each from primary squamous cell lung cancers and adenocarcinomas of the lung, and a 9th library derived from the A549 lung adenocarcinoma cell line. We assigned the identified SAGE tags to their chromosomal positions using the newly completed human genome sequence and developed a genome-wide gene expression profile representing the relative expression pattern of each transcript among the nine lung tissues. Of the 66,502 unique transcripts, 23,056 transcripts appeared more than once among all nine libraries, 18,652 (81%) of those matched to UniGene clusters while 85 tags (0.4%) matched to mitochondrial DNA/ribosomal RNA sequences. Excluding the 4,938 tags (21.4%) that matched to more than one cluster, 13,714 tags (59.5%) were linked to unique or positionally related UniGene clusters and included in the transcriptome map. The resulting transcriptome map revealed clusters of highly differentially expressed genes at specific chromosomal regions of the genome and suggested that the generation of transcriptome map using SAGE may provide a potentially powerful tool to help reveal candidate regions of chromosomal changes in lung cancer. The first phase of this project has been completed with the publication of a manuscript. We are working with CGAP to generate addtional SGAE tags to enhance the reliability of the transcriptom map and to allow better identification of chromosome regions specifically involved in NSCLC.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP010164-02
Application #
6755658
Study Section
(HGP)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Gill, R K; Yang, S-H; Meerzaman, D et al. (2011) Frequent homozygous deletion of the LKB1/STK11 gene in non-small cell lung cancer. Oncogene 30:3784-91
Ozbudak, Irem H; Shilo, Konstantin; Tavora, Fabio et al. (2009) Glucose transporter-1 in pulmonary neuroendocrine carcinomas: expression and survival analysis. Mod Pathol 22:633-8
Fukuoka, Junya; Dracheva, Tatiana; Shih, Joanna H et al. (2007) Desmoglein 3 as a prognostic factor in lung cancer. Hum Pathol 38:276-83
Hong, Kyeong-Man; Yang, Sei-Hoon; Chowdhuri, Sinchita Roy et al. (2007) Inactivation of LLC1 gene in nonsmall cell lung cancer. Int J Cancer 120:2353-8
Dracheva, Tatiana; Philip, Reena; Xiao, Wenming et al. (2007) Distinguishing lung tumours from normal lung based on a small set of genes. Lung Cancer 55:157-64
Tsurutani, Junji; Fukuoka, Junya; Tsurutani, Hiroko et al. (2006) Evaluation of two phosphorylation sites improves the prognostic significance of Akt activation in non-small-cell lung cancer tumors. J Clin Oncol 24:306-14
He, Ping; Varticovski, Lyuba; Bowman, Elise D et al. (2004) Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Hum Pathol 35:1196-209
Krop, Ian; Player, Audrey; Tablante, Ana et al. (2004) Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types. Mol Cancer Res 2:489-94
Fukuoka, Junya; Fujii, Takeshi; Shih, Joanna H et al. (2004) Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer. Clin Cancer Res 10:4314-24
Player, Audrey; Gillespie, John; Fujii, Takeshi et al. (2003) Identification of TDE2 gene and its expression in non-small cell lung cancer. Int J Cancer 107:238-43