C6-06: Gene expression signatures associated with lung adenocarcinomas in female non-smoker Chinese patients

David C. Lam, Luc Girard, Wing-Shun Chau, Issan Y. Tam, David G. Beer, Adi F. Gazdar, Lap-Ping Chung, Maria P. Wong, Wah-Kit Lam, John D. Minna
2007 Journal of Thoracic Oncology  
S378 remains unclear. We performed DNMT1 promoter luciferase assay and found that wild type p53 could negatively regulate the DNMT1 promoter, whereas mutant p53 could activate DNMT1 promoter activity. The physical binding of wild type p53 and mutant p53 to DNMT1 promoters was identified by chromatin immunoprecipitation. These data suggest that deregulation of DNMTs is associated with the loss of transcriptional repression of p53. The p53 mutation results in overexpression of DNMT1 and
more » ... DNMT1 and hypermethyaltion of target tumor suppressor genes and ultimately leads to tumorigenesis. Female-non-smokers with lung adenocarcinomas is becoming prominent among Asian patients with lung cancer. The clinical parameters of gender, smoking habits, tumor histology, ethnic origin and EGFR mutation status were identified as predictors of clinical response to targeted therapy. The aim of this study was to identify the gene expression profiles of lung adenocarcinomas compared to normal lungs, with respect to gender difference, smoking habits and tumor EGFR mutation status among Hong Kong Chinese patients with lung adenocarcinomas. Total RNA extracted from 49 lung adenocarcinomas and 9 normal lung tissues and hybridized onto Affymetrix GeneChip HG-U133 Sets. Data were normalized and subjected to repeated iterations of unsupervised hierarchical clustering, with independent validation microarray data sets, for identification of stable sample clustering, followed by supervised analysis with Significance Analysis of Microarray (SAM) and Support Vector Machine (SVM) for identification of molecular classifiers with respect to sample clustering results. Unsupervised hierarchical clustering revealed stable clustering of adenocarcinomas vs normal
doi:10.1097/01.jto.0000283228.79014.7b fatcat:6yat7oz6bbdi5dt4h2ffzue7qe