Quantitative methylation profiling of renal tumors and the discovery of a new generation of molecular markers

Abstract

Evaluation of: Gonzalgo ML, Yegnasubramanian S, Yan G et al.: Molecular profiling and classification of sporadic renal cell carcinoma by quantitative methylation analysis. Clin. Cancer Res. 10 (21), 7276–7283 (2004). This study identified RASSF1A promoter methylation as a valuable epigenetic marker for renal cancer, eventually indicating more aggressive disease. Overall, 16 gene promoters were surveyed for hypermethylation in a series of 38 renal cell tumors (comprising papillary and clear-cell renal cell carcinoma, and oncocytoma) and paired normal tissue samples. Among the target genes analyzed, RASSF1A emerged as the most frequently methylated in renal tumors and also at higher levels. Statistical analyses showed a significant association between RASSF1A promoter methylation and higher pathological stage, but not with tumor size or nuclear grade. The discriminative power of a quantitative approach allowed for a segregation between renal carcinomas and oncocytomas, using a self-organizing hierarchical neural network. These results hold the promise that epigenetic-based markers might prove clinically useful for the management of patients with renal tumors. Nevertheless, further studies, including larger sets of patients and more diversified renal tumors, as well as benign lesions, are needed to validate these preliminary results.