Combining differential expression, chromosomal and pathway analyses for the molecular characterization of renal cell carcinoma

Abstract

Using high-throughput gene-expression profiling technology, we can now gain a better understanding of the complex biology that is taking place in cancer cells. This complexity is largely dictated by the abnormal genetic makeup of the cancer cells. This abnormal genetic makeup can have profound effects on cellular activities such as cell growth, cell survival and other regulatory processes. Based on the pattern of gene expression, or molecular signatures of the tumours, we can distinguish or subclassify different types of cancers according to their cell of origin, behaviour, and the way they respond to ther-apeutic agents and radiation. These approaches will lead to better molecular subclassification of tumours, the basis of personalized medicine. We have, to date, done whole-genome microarray gene-expression profiling on several hun-dreds of kidney tumours. We adopt a combined bioinformatic approach, based on an integrative analysis of the gene-expression data. These data are used to identify both cytogenetic abnormalities and molecular pathways that are dereg-ulated in renal cell carcinoma (RCC). For example, we have identified the dereg-ulation of the VHL-hypoxia pathway in clear-cell RCC, as previously known, and the c-Myc pathway in aggressive papillary RCC. Besides the more com-mon clear-cell, papillary and chromophobe RCCs, we are currently charac-terizing the molecular signatures of rarer forms of renal neoplasia such as carcinoma of the collecting ducts, mixed epithelial and stromal tumours, chro-mosome Xp11 translocations associated with papillary RCC, renal medullary carcinoma, mucinous tubular and spindle-cell carcinoma, and a group of unclas-sified tumours. Continued development and improvement in the field of molec-ular profiling will better characterize cancer and provide more accurate diag-nosis, prognosis and prediction of drug response. © 2007 Canadian Urological Association.