Monitoring the cancer genome in plasma using circulating tumour DNA

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Published: 5 Jul 2016
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Dr Nitzan Rosenfeld - Cancer Research UK Cambridge Institute, Cambridge, UK

Dr Rosenfeld speaks with ecancertv at WIN 2016 about how liquid biopsy samples to derive circulating tumour DNA can aid in surveillance of patient response to treatment.

He outlines how circulating DNA can reflect tumour heterogeneity, differences between lesions, and record a patients' changing condition over time.

Dr Rosenfeld describes how technology and experience with genomics have enabled many clinics and private companies to derive and interpret the data gained from these samples, and how can go on to improve patient outcomes.


WIN 2016

Monitoring the cancer genome in plasma using circulating tumour DNA

Dr Nitzan Rosenfeld - Cancer Research UK Cambridge Institute, Cambridge, UK

I’ll be talking about the use of circulating tumour DNA to look at cancer genomics and how it changes over time and the different research as well as possible clinical applications for circulating tumour DNA.

Could you tell us more about circulating tumour DNA?

The amazing fact is that if you take a blood sample and you get rid of the cells you find thousands of copies of the genome present in every cc of plasma. Within this material you also find DNA that comes from the tumour, different tumour lesions in the body. Analysis of this DNA with the appropriate methods allows us to get information about the genomic changes that occur in the tumour lesions themselves.

Is tumour heterogeneity expressed through circulating DNA as well?

One of the things we are finding out is that by analysis of circulating tumour DNA in the plasma we get a picture that averages out, if you will, the different lesions that are present in the body. So we see a higher prevalence in the plasma of mutations that are present across the different lesions in the body whereas some of the private mutations that are present only in individual lesions we may miss or we may find them if these lesions are particularly large or aggressive.

Are these particularly time-bound snapshots of the genome?

One of the attractive features of circulating tumour DNA is that we obtain all this information from a plasma sample and a plasma sample is minimally invasive, you can obtain it multiple times during the patient’s course of treatment, and this allows us to obtain time courses. Initially these time courses were only of individual mutations that we could analyse but more and more we can now use the same material to look at large extensive profiles. This allows us to get extensive profiles and how these change over time.

Do the liquid biopsies require newer equipment or technology?

The way we manage to get the information out of the liquid biopsies, if you will, is by integrating technologies that have been maturing and in existence by improving them and integrating them in a way that is more effective. So the separation of the plasma from the blood is not new, the extraction of DNA from plasma is something that’s been around for many years. Taking this DNA and using this to generate libraries from next generation sequencing and then applying the right methods for that and the right methods of analysis allows us to really drill deeper and deeper in terms of sensitivity and also in terms of breadth of analysis.

Is this beyond some clinics’ capacity?

The information is there and it’s definitely doable and obtainable but it does require expertise and a certain degree of dedication to the task, if you will. So the best ways to access that are either through collaborating with academic labs that specialise in this or more and more it’s now becoming available as a commercial service through centres or companies that specialise in providing this type of service. I should add that I am personally a co-founder of one of these companies so I have a conflict of interest in this.

How does having a personalised genomic treatment impact a patient?

What we hope is that the accessibility, the ease of collection of these samples, will mean that it would be possible to obtain the types of genomic analyses for more and more patients at multiple time points and, in a way, to make genomic analysis more and more accessible to patients. Data is still accumulating to really delineate and find the clinical validity and clinical utility of these tests. Of course in order for this to be commercially available it needs to be set at the right price points and reimbursements in all these systems. But in terms of accessibility it’s coming fast.