Jiang Feng, Yin Zhengnan, Caraway Nancy P, Li Ruiyun, Katz Ruth L
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Neoplasia. 2004 Sep-Oct;6(5):623-35. doi: 10.1593/neo.04142.
To investigate the genomic aberrations that are involved in lung tumorigenesis and therefore may be developed as biomarkers for lung cancer diagnosis, we characterized the genomic copy number changes associated with individual genes in 14 tumors from patients with primary non small cell lung cancer (NSCLC). Six squamous cell carcinomas (SQCAs) and eight adenocarcinomas (ADCAs) were examined by high-resolution comparative genomic hybridization (CGH) analysis of cDNA microarray. The SQCAs and ADCAs shared common frequency distributions of recurrent genomic gains of 63 genes and losses of 72 genes. Cluster analysis using 57 genes defined the genomic differences between these two major histologic types of NSCLC. Genomic aberrations from a set of 18 genes showed distinct difference of primary ADCAs from their paired normal lung tissues. The genomic copy number of four genes was validated by fluorescence in situ hybridization of 32 primary NSCLC tumors, including those used for cDNA microarray CGH analysis; a strong correlation with cDNA microarray CGH data emerged. The identified genomic aberrations may be involved in the initiation and progression of lung tumorigenesis and, most importantly, may be developed as new biomarkers for the early detection and classification of lung cancer.
为了研究参与肺癌发生发展、因而有可能被开发为肺癌诊断生物标志物的基因组畸变，我们对14例原发性非小细胞肺癌（NSCLC）患者肿瘤中与单个基因相关的基因组拷贝数变化进行了特征分析。通过对cDNA微阵列进行高分辨率比较基因组杂交（CGH）分析，检测了6例鳞状细胞癌（SQCA）和8例腺癌（ADCA）。SQCA和ADCA在63个基因的反复基因组增益和72个基因的缺失方面具有共同的频率分布。使用57个基因进行的聚类分析确定了这两种主要组织学类型NSCLC之间的基因组差异。一组18个基因的基因组畸变显示原发性ADCA与其配对的正常肺组织存在明显差异。通过对32例原发性NSCLC肿瘤（包括用于cDNA微阵列CGH分析的肿瘤）进行荧光原位杂交，验证了4个基因的基因组拷贝数；结果显示与cDNA微阵列CGH数据具有很强的相关性。所鉴定的基因组畸变可能参与肺癌发生的起始和进展，最重要的是，有可能被开发为肺癌早期检测和分类的新生物标志物。
