A landmark study published in the New England Journal of Medicine may help explain why identifying biomarkers for personalized cancer treatments through single biopsies have not been more successful.
Scientists performed the first genome-wide analysis of the genetic variation between different regions of the same tumor using kidney cancer samples donated by patients with advanced kidney cancer and treated at the Royal Marsden Hospital under the supervision of Dr James Larkin. It was discovered that the majority (around two-thirds of gene faults) were not shared among other biopsies from the same tumor.
Lead author professor Charles Swanton, from Cancer Research UK’s London Research Institute and the UCL Cancer Institute, said, “We’ve known for some time that tumors are a ‘patchwork’ of faults, but this is the first time we’ve been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumor in such exquisite detail.
“This has revealed an extraordinary amount of diversity, with more differences between biopsies from the same tumor at the genetic level than there are similarities. The next step will be to understand what’s driving this diversity in different cancers and identify key driver mutations that are common throughout all parts of a tumor.”
Sample genetic faults removed from different parts of 4 separate kidney tumors and genetic faults from sites where the cancer had metastasized were compared.
Scientists were able to identify 118 different mutations.
- 40 were found in all biopsies
- 53 were present in most but not all biopsies
- 25 were only detected in a single biopsy
According to Dr Larkin, “This study in kidney cancer has shown significant molecular changes between different parts of the same tumor. We have also seen differences between primary kidney tumors and cancer cells that have spread to other organs. This may 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 tumor.”
Researchers were able to trace the origins of particular subtypes of cancer cells back to key driver mutations by analyzing the location of shared mutations in relation to the whole tumor. Thus, researchers created an evolutionary ‘map’ showing genetic changes within the tumor over time.
Cancer Research UK’s chief clinician, Professor Peter Johnson, said, “These findings highlight important differences that exist within tumors and suggest a way to improve the success rate of personalized cancer medicines.
“We are now planning to see if these results can be replicated in larger groups of patients…using the latest high-tech gene sequencing machines to track down the genetic faults driving different types of cancer.”
Source: Cancer Research UK.