Chordoma is a rare bone tumour for which surgery and radiotherapy are the only treatment options currently available. After treatment, patients are followed up using scans at regular intervals to monitor for disease relapse, as early treatment of recurrence offers the best chance of a good prognosis.

Dr Katherine Trevers, working with Professor Adrienne Flanagan at University College London, was awarded an Idea Grant by the Bone Cancer Research Trust, to develop a test which will allow patients with chordoma to be monitored using a non-invasive blood test, instead of regular scans. If successful, a blood test could be used to reduce the number of scans. If a blood test were positive: the scan would confirm the result of the blood test and importantly also identify where the tumour had relapsed (at the site of the original tumour or metastatic disease) to plan treatment. A blood test could also be used for measuring the effect of a new treatment in future clinical trials for chordoma

Aims and results of the study

Our DNA contains a full library of genes in every cell and carries the instructions for all the development and function of our bodies.

However, genes are not always required to be working, or can be working at different levels. When a gene is “working” its instructions are copied into and “expressed” as an RNA molecule that carries the instructions from genes to produce the specific proteins necessary for cellular processes.

Most RNA is present inside cells; however, some is shed into the bloodstream. RNA that is found in the circulation is known as cell free RNA (cfRNA). Normal and cancer cells both shed cfRNA and it has been shown that large or more advanced tumours shed more cfRNA than smaller tumours.

Chordoma cells express a gene called brachyury, also known as TBTX , which is normally only working (expressed) in the embryo. Expression of this gene in adults is highly associated with chordoma. Other genes such as SOX9 and HOPX are also expressed by chordoma cells.

The premise of this research is that detection of these genes in cfRNA, from a blood sample would support the presence of chordoma.

The research team had access to blood samples from healthy individuals (volunteers) and from chordoma patients participating in the Understanding Chordoma National Cohort study, which opened in January 2018; with about 150 patients recruited, this is the largest study of chordoma patients to date in the world.

They aimed to investigate the presence of 11 genes known to be associated with chordoma and determine if they could be used as biomarkers for the disease.

Although they could detect TBTX in chordoma blood, it could only be detected at a very low level, even in patients with very large tumours. Unfortunately, this means that the approach used is not sensitive enough to detect and monitor chordoma patients who might have small tumours that are forming as a recurrence.

Even though the assay is not currently sensitive enough, it is very interesting and potentially valuable to know that TBTX cfRNA can be detected in chordoma blood. As technology evolves, they will continue to monitor and test out new approaches that may be more sensitive to detect TBTX in blood samples, in the hope that an assay can be developed in the future to monitor chordoma patients.

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