Taking one biopsy sample of a tumor may not be enough to reveal its full genetic identity, according to a breakthrough Cancer Research UK study published in the New England Journal of Medicine on Friday 8 March. The study is significant because it suggests relying on one sample could overlook important biomarkers that help make tailored treatments effective, explaining perhaps why personalized cancer therapy has been less successful than expected. Professor Peter Johnson, chief clinician at Cancer Research UK said in a statement that the study highlights \"important differences that exist within tumours and suggest a way to improve the success rate of personalised cancer medicines\". The lead author of the study is Professor Charles Swanton, who works at Cancer Research UK\'s London Research Institute and the UCL Cancer Institute. He and his colleagues analyzed the genetic variation among different regions of the same cancer tumor, using samples donated by patients with advanced kidney cancer. This is the first time genome-wide analysis has been used for this. Swanton told the press that scientists have known for a while that a tumor is a \"patchwork\" of faults, but this is the first time, thanks to cutting edge genomic sequencing technology, scientists have been able to map the genetic landscape of a tumor in such \"exquisite detail\". For the study, he and his colleagues compared the genetic variations in samples taken from different regions of four separate kidney tumors. They also took samples from other organs the cancer had spread to. They found that about two thirds of the genetic faults in a tumor were not repeated across other biopsy samples from the same tumor. They uncovered 118 different mutations: 40 were \"ubiquitous mutations\", that is they were present in all the biopsy samples, 53 were \"shared mutations\", that is they were present in more than one, but not all of the samples, and 25 were \"private mutations\", that were only found in a single biopsy. \"This has revealed an extraordinary amount of diversity, with more differences between biopsies from the same tumour at the genetic level than there are similarities,\" said Swanton. The patients who donated the samples used in the study were being treated at London\'s Royal Marsden Hospital under the supervision of co-author Dr James Larkin. Larkin said the study has implications for personalized medicine, which tailors treatment for individual patients. The results show there are significant molecular differences across the various parts of a tumor, and also reveals differences between primary tumors and cancer cells that have spread to other sites. He said such findings could be \"relevant to how we treat kidney cancer with drugs because the molecular changes that drive the growth of the cancer once it has spread may be different from those that drive the growth of the primary tumour.\" The researchers also analyzed the location of the shared mutations in relation to the whole tumor. From this they traced the origin of particular subtypes of cancer cells, to identify key driver mutations to make a \"map\" of how the gene variations in the tumor may have evolved. Swanton said this is the first time they have been able to use the pattern of genetic faults in a tumor to find the origins of certain cancer cell populations. He said it was like Charles Darwin\'s \"tree of life\" that shows how different species are related. The key is to find the mutations in the \"trunk\" of the tree, because these are the common ones, as opposed to those in the remote branches, which may only be present in a minority of cancer cells. Such an approach may \"also explain why surgery to remove the primary kidney tumour can improve survival, by decreasing the likelihood that resistant cells will be present that could go on to re-grow the tumour after treatment,\" said Swanton. Johnson said under Cancer Research UK\'s Genomics Initiative they are going to see if the same results occur with larger groups of patients. The Initiative is a series of groundbreaking projects where scientists will use the latest high-tech gene sequencing machines to track down the genetic faults driving different types of cancer. The study was funded by Cancer Research UK, the Medical Research Council and the Wellcome Trust.