Genomic alterations of chromosome region 11p as predictive marker by array comparative genomic hybridization in lung adenocarcinoma patients

Abstract

Array comparative genomic hybridization (aCGH) provides a method to quantitatively measure the changes of DNA copy number with an extremely high resolution and to map them directly onto the complete linear genome sequences. In this study, we used aCGH to compare genomic alterations in fresh-frozen lung cancer tissues of 21 adenocarcinomas (AdCCs) (11 early relapse and 10 nonrelapse) and identified genomic alterations that showed significant by different frequency between early relapse and nonrelapse AdCCs. Twelve clones were identified by the false discovery rate (FDR) test, and Kaplan-Meier analyses were selected as predictive markers. The significant gain clones were found in 11p (11p15.4, 11p15.1, and 11p13). When the cutoff value was 2, study of the association between candidate clones and relapse prediction revealed that early relapse and nonrelapse groups were most effectively separated. To further validate the gain of chromosome 11p region that was identified by array CGH, fluorescence in situ hybridization (FISH) was performed. To further confirm the results of aCGH, copy number changes of cancer-related candidate genes in AdCC patients were compared by real-time quantitative polymerase chain reaction. Array CGH and real-time quantitative polymerase chain reaction data were found to correspond to delineated DNA copy number changes. Genomic alterations of chromosome 11p region in AdCC patients were observed with aCGH, and a relapsable marker was identified in the nonrelapse group. This marker could be useful in stratifying patient groups according to likelihood of relapse for adjuvant treatment after surgical resection.