Potential role of blood testing for microRNA profiles in paediatric cancers

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Published: 11 Nov 2014
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Dr Matthew Murray - University of Cambridge, Cambridge, UK

Dr Murray talks to ecancertv at NCRI 2014 about how changes in small pieces of genetic code in malignant germ cell tumours can be found in the blood stream, and how this work has been extended to common solid tumours of childhood, with the aim to assist diagnosis and personalise treatment.

What we’ve previously shown is changes in small pieces of genetic code in one area of children’s cancer, in paediatric germ cell tumours, we’ve taken those findings and shown that we can find the sane pieces of genetic code in the bloodstream of patients at the time of diagnosis in germ cell tumours and we’ve previously published that work. What we went on to hypothesise was whether we could find different pieces of genetic code in individual tumour types in childhood at the time of diagnosis. So what we did was we recruited patients in Cambridge to the study; we used their blood-based systems, we used what we call serum, based from the blood at the time of diagnosis, and were able to extract RNA from those samples and then do comprehensive profiling of all the known microRNAs as we call them, the small pieces of genetic code in the bloodstream, and identify differences in different children’s tumour types and identify fingerprints, or signatures, that we might be able to use in the future.

So it’s quite a small study, it was a hypothesis generational study to see whether this approach was feasible. So it was a single centre study rather than being something larger. We looked at a total of 54 patients, that included 34 patients who had cancer, but we also, importantly, looked at 20 children who were age and gender matched who did not have a diagnosis of cancer so that we could compare not only between different types of children’s cancer but with other control samples to know that the signatures we were getting were unique for those individual tumours. So the findings are quite early but it shows that it’s feasible to do, that we can reliably detect RNA, that we also identified other methods for a pipeline analysis which involves quality control steps to make sure that our findings are robust and reproducible as well as identify the fingerprints themselves. So it will now be important for those initial findings to be replicated in larger, independent studies involving a greater number of patients. We may be able to refine those fingerprints further to the smallest diagnostic set of microRNAs in the bloodstream that can reliably distinguish between different tumour types.

Will there be certain people that will benefit from this?

We have the possibility in a range of common childhood tumours such as sarcoma types: Wilms’ tumour, hepatoblastoma, neuroblastoma, to benefit. One of the most striking findings we found was a difference between patients with neuroblastoma. Neuroblastoma affects about 100 children every year in the UK with a new diagnosis and it’s a spectrum of disease that ranges from some patients with very benign disease which isn’t very aggressive, associated with good outcomes, to some children who have very aggressive disease characterised by biological changes. What we found was that there were some very striking differences in the patients who had high risk neuroblastoma, which was characterised by amplification of a gene called MYCN, compared to those patients who had low risk disease without the amplification of that gene. That offers the potential not only that these microRNAs in the bloodstream at diagnosis may be useful to help with diagnosis, perhaps avoiding surgery in difficult to access tumours, but also that the profiles may also be able to help us identify risk in patients between those who may do well and those who may do less well and may also up-front in the future be able to distinguish what sort of treatment different patients should have with neuroblastoma.

At the moment, as I say, we’re presenting this work as a poster. It’s very new in that it’s an extension of the work we’ve done previously in germ cell tumours but across a range of childhood cancers. So we’ve been talking to a large number of national and international children’s cancer groups, for example the Rhabdomyosarcoma Group, the Wilms’ Tumour Group, who have got a current CRUK funded import study which is currently on-going which is collecting blood-based and urine samples at the time of diagnosis for children with renal tumours, the majority of which are Wilms’ tumour. What we’re doing is having an initial dialogue about how some of these studies may be set up as part of future international clinical trials which will enrol large numbers of patients and may be able to help answer these questions more definitively about which are the smallest sub-types or signatures that we identify in the blood stream that can reliably diagnose disease and may also in the future be able to be used for disease monitoring and detection, perhaps, of recurrence.