Principal Investigators: 

Dr Tim Forshew

Award Amount: 
6 months

Project Summary

It has been established that certain high grade tumours release mutant DNA into the blood and that this can be used to monitor response to therapy, and to detect early recurrence of disease.  Dr Forshew was the first to prove that it’s possible to read large parts of this faulty DNA from the blood and was involved in the largest study on this new test in patients with breast cancer.  He will now apply these skills to bone and soft tissue sarcomas and low grade connective tissue tumours, using a large collection of bio-banked samples at UCL.  They will take this work forward and test if the fault DNA that occurs in benign and low-grade tumours can also be detected in the blood of patients.

The team will analyse the DNA of low-grade bone and soft tissue tumours for frequently occurring mutations.  If mutations are found they will gather data, which will allow them to progress onto larger research project in a clinical setting.

The potential benefit of this work is that if this approach is found to be successful for detecting faulty DNA from low grade tumours in a patient’s blood, it would mean that a simple blood test could be used to monitor these tumour types.  This could be used to monitor patients for recurrence of disease, and there relevant in some tumour types, for response to treatment.  An advantage of a blood test is that it could be performed by a GP rather than visiting a hospital.  It may also be cost efficient, if it allows us to reduce the need for expensive tests such as x-rays and CT scans.

End of Project Summary

This study has been highly successful. We have developed digital PCR assays for all 14 hotspot mutations originally planned and tested 13 of these. We have shown that using these assays we are able to detect and quantify cancer DNA in the blood stream of select individuals with both chondrosarcoma (CS) and giant cell tumour of bone (GCT). We have also validated both the IDH1 and H3F3A assays in large numbers of FFPE tumour samples in order to use them for tissue-based diagnostics. Finally we have developed capture-based sequencing techniques as a means of identifying common sarcoma breakpoints in tumour tissue and have demonstrated successfully the detection of breakpoints in FFPE samples.  We are now testing the ability to find these breakpoints and additional structural variants and point mutations in blood samples

Future research

We are continuing to collect serial blood samples from patients with sarcoma throughout the course of patients treatment at RNOH and have increased the volume of blood collected from 10 to 30ml where feasible. We are continuing to use the digital PCR assays developed in this study to assess additional patients. By correlating our findings with detailed clinical information we will assess the utility of ctDNA for clinical applications including molecular stratification, prognostication and relapse detection. In addition we are continuing to test and develop new methods for ctDNA detection such as deep next generation sequencing.



  • Gutteridge, A. et al. (2017) Digital PCR analysis of circulating tumour DMA: a biomarker for chondrosarcoma diagnossi, prognostication and residual disease detection. Cancer Medicine 6(10). Read more:


  • Rathbone, V. M. et al. Development of Diagnostic Test for H3F3A p.Gly34Try (G34W) Mutation in Giant Cell Tumours of Bone Based on Droplet Digital PCR. Poster presented at Dublin Pathology 2015. June, 2015. Dublin, UK
  • Gutteridge, A. et al. IDH1 and IDH2 digital PCR assay development for chondrosarcoma tissue and plasma analysis. Poster presented at the Dublin Pathology 2015. June, 2015. Dublin, UK.

Presentations & Workshops

  • Sequencing and dPCR analysis of circulating tumour DNA. The challenges and potential applications of liquid biopsy analysis. Presentation as the Keynote Speaker given at the New Zealand Next Generation Sequencing Conference. 2015. New Zealand.
  • NGS and dPCR Analysis of Circulating Tumour DNA and Their Potential uses in Cancer Patient Care. Presentation given at the qPCR & NGS. Advances Molecular Diagnostics for Biomarker Discovery. 2015. Germany.
  • Rathbone, V. Presentation given at the join BDIAP and Pathology Society. June, 2016. Nottingham, UK.

Further Funding

  • Further funding of £69,963 was secured from the Bone Cancer Research Trust. For project entitled: Does circulating DNA predict the grade and disease burden of chondrosarcoma? A nationwide collaboration for primary bone tumour research. 2017.


  • Dr Tim Forshew was the keynote speaker at the New Zealand Next Generation Sequencing Conference, 2015.
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