陣列比较基因组杂交技术.docVIP

肾透明细胞癌遗传聚类的阵列比较基因组杂交技术： DNA甲基化与肾癌患者预后之间的关系（Genetic Clustering of Clear Cell Renal Cell Carcinoma Based on Array-Comparative Genomic Hybridization: Its Association with DNA Methylation Alteration and Patient Outcome） Abstract Purpose:The aim of this study was to clarify genetic and epigenetic alterations occurring during renal carcinogenesis. Experimental Design: Copy number alterations were examined by array-based comparative genomic hybridization analysis using an array harboring 4,361bacterial artificial chromosome clones, and DNA methylation alterations on CpG islands of the p16, human MutL homologue 1,von Hippel-Lindau,and thrombospondin 1 genes and the methylated in tumor (MINT-1, MINT-2, MINT-12, MINT-25, and MINT-31) clones were examined in 51clear cell renal cell carcinomas(RCC). Results: By unsupervised hierarchical clustering analysis based on copy number alterations,clear cell RCCs were clustered into the two subclasses, clusters A (n =34)andB(n =17).Copy number alterations were accumulated in cluster B. Loss of chromosome 3p and gain of 5q and 7 were frequent in both clusters A and B, whereas loss of1p, 4, 9,13q, and14q was frequent only in cluster B. The average number of methylated CpGislands in cluster B was significantly higher than those in clusterA. Clear cell RCCs showing higher histologic grades, vascular involvement, renal vein tumor thrombi, and higher pathologic stages were accumulated in cluster B.The recur-rence-free and overall survival rates of patients in cluster B were significantly lower than those of patients in cluster A. Multivariate analysis revealed that genetic clustering was a predictor of recurrence-free survival and was independent of histologic grade and pathologic stage. Conclusions: This genetic clustering of clear cell RCC is significantly associated with regional DNA hypermethylation and may become a prognostic indicator for patients with RCC. Key words: RCC Genetic Clustering Array-Comparative Genomic Hybridizati