Following the initial survey of 101 samples, the researchers examined those genes found to be mutated in a further 300 samples to further clarify the potential importance of mutations in ccRCC.

"Systematic genetic analyses have the power to unmask previously unknown drivers in human cancer and the biology they impact", says Dr Bin Teh, Head of the Laboratory of Cancer Genetics at the Van Andel Research Institute, Grand Rapids, Michigan, USA. "Such knowledge is critical to improvements in the diagnosis and treatment of cancer."

Delineation of the genetic foundation of ccRCC will ultimately help in diagnosis and in selection of treatment: the data show that, on the basis of genetic lesions, even apparently homogeneous cancers can be begin to be classified into subtypes that display distinctive biological features driven by specific mutations.

There has been some success in exploiting one driver mutation in ccRCC, VHL, in therapeutic approaches - the most productive means to discover new biological understanding of this enigmatic cancer has been genetics - and more will be needed.

"Even in a tumour type dominated by single histology, with a prevalent signature, even in this 'clearest' of cases, we see evidence for substantial genetic heterogeneity," explains Dr Futreal. "In this large set of 100 ccRCC samples, some mutations are found only once or twice and so we are likely to have missed others.

"To search comprehensively - to build the full picture we need of cancer genetics - we will need many hundred samples sequenced through the entire genome and all genes. The target for those cancers being analysed by the International Cancer Genome Consortium is 500. This is the scale that will be required to really take this group of diseases apart."

Source: Wellcome Trust Sanger Institute