Elsevier

European Urology

Volume 63, Issue 5, May 2013, Pages 855-857
European Urology

Platinum Priority – Editorial and Reply from Authors
Referring to the article published on pp. 848–854 of this issue
The Changing Face of Renal Cell Carcinoma: The Impact of Systematic Genetic Sequencing on Our Understanding of This Tumor's Biology

https://doi.org/10.1016/j.eururo.2012.09.049Get rights and content

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Hereditary renal cancer and the von Hippel-Lindau syndrome

With regard to urologic oncology, this need for hereditary syndromes mostly limited mutational interest to renal cell carcinoma (RCC). This tumor occurs in a variety of hereditary cancer syndromes, and for each, a causative gene or genes have now been identified. For example, inherited mutations of the von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase (VHL) gene were first reported in 1993 following karyotyping studies revealing its genetic location [2]. Subsequently, met

Mutational screening in renal cancer and histone methylation

The identification of the VHL gene and its role in hypoxia has dominated basic research into RCC from its discovery until recent years. Mutational and functional studies focused on the HIF transcriptional factors and putative target genes with HREs. When few additional mutations were identified, workers switched to a more systematic approach to this cancer. In 2009–2010, a screen of 3544 protein-coding genes in 101 cases of ccRCC was reported [5], [6]. Five new frequently mutated genes were

Mutations of histone regulators in sporadic renal cancer

These observations have moved biologic interest in ccRCC from hypoxia (and VHL) to epigenetic gene regulation (and, specifically, the methylation of histone 3 and chromatin structure). It is known that dysregulation of epigenetic gene control is important in many human cancers including renal carcinoma. In this month's European Urology, Hakimi et al. follow these initial reports with an independent validation in a large ccRCC cohort [11]. The authors use Sanger sequencing to identify mutations

The future

Although this report furthers our understanding of the biology of ccRCC, there are still many gaps to fill. For example, what of the 35% of cancers without a mutation in one of these genes? Most sequencing efforts to date have looked at coding gene exons or expressed RNA. We await reports of whole genome studies to fill in these missing regions. What are the implications of these findings for targeted therapy in patients with advanced ccRCC? The paradigm of this approach to date has been this

Conflicts of interest

The authors have nothing to disclose.

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