16 June 2015
Scientists have described a new ‘Google map’ approach for studying the cancer genome, which allows them to zoom in and out on the small and large scale changes that define individual cancers.
The University of Winconsin-Madison team’s approach, which combines both optical mapping with DNA sequencing, has enabled the researchers to uncover extensive genomic variation within a multiple myeloma patient.
Senior study author Prof David Schwartz said: “Cancer genomes are complicated but we found that, using an approach like this, you can begin to understand them at every level”.
Published in the Proceedings of the National Academy of Sciences, the scientists hope the new integrated approach is a step towards the new era of personalised medicine.
Study co-author Prof Fotis Asimakopoulos said: "To cure myeloma, we need to understand how genomes evolve with progression and treatment…the more we can understand the drivers in cancer in significant depth, and in each individual, the better we can tailor treatment to each patient's disease biology".
The research team isolated DNA from normal and cancerous tissue from a patient with multiple myeloma at two stages: firstly when the cancer was responsive to drug treatment, and also after it had progressed and was resistant to chemotherapy. To gain the ‘zoomed in’ portion of the genome the researchers carried out DNA sequencing. Following this, optical mapping was carried out to obtain the ‘zoomed out’ view. The research team then layered the two together to get a full map of the patient’s multiple myeloma genome.
Widespread structural variations, along with notable mutations, were found by the researchers in the multiple myeloma genome, compared to the patient’s normal genome. Additionally, there was an increase in number and range of genetic mutations observed following tumour progression.
Significantly, the study was limited because it only involved one patient tumour; however, it provides a useful example of the new approach, showing a comprehensive analysis of genome variation, particularly structural variation, alongside an in-depth view of genomic variation at single base pair and chromosomal levels.
The researchers have highlighted the changes that they believe have potential as future drug targets and should be explored further. It is hoped the new approach will allow scientists to explore how cancers develop drug resistance and find solutions to this problem.
Looking to the future, Schwartz hopes to use the approach to map individual patient cancer genomes over the course of their disease. Ultimately he would like to advance the system so it is capable of analysing 1000 genomes in 24 hours.