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Molecular Profiling and Classification of Sporadic Renal Cell Carcinoma by Quantitative Methylation Analysis

2004; American Association for Cancer Research; Volume: 10; Issue: 21 Linguagem: Inglês

10.1158/1078-0432.ccr-03-0692

1557-3265

Mark L. Gonzalgo, Srinivasan Yegnasubramanian, Gai Yan, Craig Rogers, Theresa L. Nicol, William G. Nelson, Christian P. Pavlovich,

Renal and related cancers

Preoperative histologic classification of solid renal masses remains limited with current technology. We determine the utility of molecular profiling based on quantitative methylation analysis for characterization of sporadic renal cell carcinoma.Primary renal cell carcinomas representing three different histologic subtypes were obtained from a total of 38 patients who underwent radical nephrectomy for suspected malignant disease. Genomic DNA was isolated from tumors and was subjected to sodium bisulfite modification. The normalized index of methylation (NIM) for each sample was determined by quantitative real-time methylation-specific PCR at 17 different gene promoters. Hierarchical cluster analysis was performed by using an unsupervised neural network with binary tree topology.The majority of gene promoters that were analyzed in this study demonstrated very low levels of methylation (NIM 1% methylation (mean NIM = 0.11). Hierarchical cluster analysis based on quantitative methylation levels resulted in stratification of sporadic renal cell carcinomas into their discrete histologic subtypes.Classification of sporadic renal cell carcinomas into histologic subtypes can be accomplished via multigene quantitative methylation profiling. Validation of this approach and selection of appropriate methylation markers may ultimately lead to use of this technology in the preoperative assessment of suspicious renal masses.