Cancer is the ultimate disorder of the genome, characterised not by just one or two mutations, but by hundreds to thousands of acquired mutations that have been accrued through the development of a tumour. Thanks to the recent increase in the speed of sequencing offered by modern sequencing technologies, we are no longer restricted to exploring tiny fragments of protein-coding portions of the human genome. We can now read all the genetic material in human cells. Here, the framework of a next-generation sequencing experiment is explained, giving insight into the advances and difficulties posed by processing the enormous datasets generated through these methods. Some of the recent insights into tumour biology, that exploit the extraordinary surge in scale and the digital nature of next-generation sequencing, are highlighted, including cancer gene discovery, the detection of mutation signatures and cancer evolution. Technological and intellectual developments are starting to shape the personalized cancer genomic profiles of tomorrow. Let's train the next-generation of clinicians to be able to read them from today.
Keywords: Cancer genomics; cancer evolution; cancer genes; mutation signatures; next-generation sequencing; tumour heterogeneity.
© 2014 Royal College of Physicians.