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(Chest. 2004;125:97S.)
© 2004 American College of Chest Physicians

Serial Analysis of Gene Expression Profiles of Developmental Stages in Non-small Cell Lung Carcinoma*

Calum MacAulay, PhD; Kim Lonergan, PhD; Bryan Chi, BSc; Scott Zuyderduyn, BSc; Jaquie Shein, MSc; Ming Tsao, MD; Jean LeRiche, MD; Steven Jones, PhD; Marco Marra, PhD; Stephen Lam, MD and Wan L. Lam, PhD

* From the Departments of Cancer Imaging (Drs. MacAulay and S. Lam), Cancer Genetics (Drs. Lonergan, Chi, and W.L. Lam), Canada’s Michael Smith Genome Science Centre, BC Cancer Agency (Drs. Zuyderduyn, Shein, Jones, and Marra); Cancer Imaging, BC Cancer Agency (Dr. LeRiche), Vancouver, BC, Canada, and the Ontario Cancer Institute (Dr. Tsao), Princess Margaret Hospital, Toronto, ON, Canada.

Correspondence to: Calum MacAulay, PhD, Head, Cancer Imaging Department, BC Cancer Research Centre/BC Cancer Agency, 601 W 10th Ave, Vancouver, BC, Canada V5Z 1L3; e-mail: cmacaula{at}bccancer.bc.ca

Identifying genes and pathways that are critical to early lung cancer progression (ie, interepithelial neoplasia) would facilitate early detection, chemoprevention strategies, and intervention.

The objective of this study was to identify such pathways through expression profiling. We constructed multiple serial analysis of gene expression (SAGE) libraries to describe gene expression in normal lung epithelial cells, carcinoma in situ, and invasive squamous cell lung cancer. By comparing these profiles, we have identified the changes that accompany the transitions between these progression stages.

All specimens used for library construction in this study were acquired by autofluorescence bronchoscopy-directed bronchial brushings and biopsies or during surgical resection. Libraries were constructed according to the MircoSAGE protocol. Simple expression-level analyses have been performed on mass and for selected subsets of genes.

A total of 15 SAGE libraries have been analyzed to date. These were generated from carcinoma in situ, squamous cell carcinoma, and brushings from normal lung epithelium. Greater than 60,000 tags have been sequenced for each library, collectively comprising approximately 133,000 unique tags. Comparisons of normalized libraries yielded information on the following: (1) lung SAGE repeatability and subject sensitivity; (2) cell selection issues; (3) transcripts unique to lung tissue or lung neoplasia; and (4) biological functions affected in disease progression.

We have demonstrated the ability to generate and compare SAGE libraries derived from minute clinical specimens. Identification genes and pathways that are key to tumor progression can direct diagnosis and treatment in accordance with the biology of lung cancer.


   Footnotes
 
Abbreviation: SAGE = serial analysis of gene expression





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