FNAseq: Nanopore sequencing of FNA samples in thyroid cancer

Dr Hannah Nieto, Thyroid Cancer Research Group, Institute of Metabolism and Systems Research, University of Birmingham

The diagnosis of whether a patient has thyroid cancer or not is currently dependent on a combination of clinical evaluation, ultrasonography and fine needle aspiration cytology (FNAc). A significant proportion of thyroid nodules are difficult to diagnose following these tests and fall in an indeterminate category in which the likelihood of malignancy is uncertain. Most of these nodules are benign but patients generally have to undergo thyroid surgery so the nodule can be examined histopathologically. A number of centres use molecular biomarkers in FNAc specimens to try and determine if a thyroid nodule is malignant based on molecular characteristics of the thyroid cells.

Sequencing of the genetic material in these cells is one of the approaches currently used in the US and in Europe but this is not routinely available in most UK centres and has not been adopted universally. In addition, the analysis of the genetic make-up of these tumour cells helps predict the likely future behaviour of the tumour and therefore how aggressively we should treat it and possibly which additional therapies may be used in those tumours that do not respond to standard treatment. This would avoid unnecessary anxiety for patients as well as unnecessary surgery for some and more appropriate targeted and individualised treatment for others.

It is not currently possible to sequence the genetic material from fine needle aspirates quickly. In order to do this they have to be sent to specialised sequencing facilities which is cumbersome and expensive. We propose to explore a new technology which could revolutionise thyroid cancer treatment. 

The MinION nanopore DNA sequencer is a tiny, lightweight and portable device which could be brought into the clinic room to be used in a one-stop thyroid clinic to rapidly determine the genetic molecular make-up of the thyroid nodule. The proposed technique and equipment have been used successfully in the rapid diagnosis of other cancers and of infectious diseases such as during the Ebola epidemic.

Our project will appraise the exciting possibility of using nanopore sequencers to differentiate benign from malignant thyroid lesions. Successful progress would open the door for patients to be diagnosed in a single day, obviating unnecessary surgery, repeated hospital trips and anxiety, whilst also targeting individualised treatments to those patients who need them.

Progress report  2023

What are the results of your study so far?

So far, we have successfully sequenced both cell culture (cells grown in vitro) samples and patient samples, after the DNA has been amplified using whole genome amplification. This is very exciting as, to our knowledge, this has never been done in thyroid cancer before.

The nanopore has now also been successfully established in our laboratory, allowing in-house sequencing, and facilitating our ongoing work with Adaptive Sampling – this is a bioinformatic technique used to focus where the sequencing is undertaken (i.e. to target certain genes) to make the process even quicker and more cost-effective to run.  

What could the results mean for patients?

We are very hopeful this could change the face of diagnostics in thyroid cancer. Being able to more accurately determine the likelihood of thyroid cancer can direct how much treatment would need. It could help determine whether hemithyroidectomy (partial thyroid removal) or total thyroidectomy (full removal) is required, and whether the patient is likely to need radioiodine treatment or not.

How has the BTF Research Award made a difference?

The BTF Research Award has allowed us to undertake this research, to investigate how we can use genetic sequencing in thyroid cancer in the UK, and move towards efficient technology we can adapt for use in the NHS. This project has also inspired a project in anaplastic thyroid cancer, looking at how we can sequence drug-targetable mutations to allow patients faster access to personalised therapy. 

Thank you to the BTF for this critical funding. Since the BTF award we have taken this project forward and I have been awarded the very prestigious Academy of Medical Sciences Starter Grant Award. This will allow us to develop adaptive sampling and the aim is to take this forward in a clinical pilot study. 

Please read the progress report  - December 2019

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