Endocrine Abstracts

Introduction: Liquid biopsies have revolutionised cancer care, from accurate diagnosis to guiding treatment and surveillance. Here, we used shallow Whole Genome Sequencing (sWGS); a cost-effective and easy-to-perform test to explore concordance of copy number alterations (CNAs) between formalin-fixed paraffin-embedded (FFPE) tissue extracted DNA and circulating cell-free DNA (cfDNA) in patients with Thyroid Cancer (TC) during different stages of the disease.

Aim: To explore the utilisation of sWGS as an aiding tool in the monitoring of TC by looking at concordance of CNAs between FFPEs and cfDNA during follow up.

Methods: FFPE and cfDNA of 23 patients during different stages of TC (pre-operative, remission, progression, new metastases and recurrence) were examined for the presence of CNAs using the Ion ReproSeq PGS™ platform.

Results: Twelve FFPE DNA samples had clear CNAs on sWGS. We applied the same test to the relevant patients’ cfDNA looking for CNAs. At the time of writing, all remission cfDNA samples (n =8) were negative for CNAs. One patient had matching CNAs in FFPE DNA and cfDNA during progressive disease. There were 2 further patients with disease progression but without clear CNAs in cfDNA. Further sWGS is underway on the remaining cfDNA samples of patients with positive CNAs on FFPE DNA.

Discussion: Almost half of FFPE DNA showed no clear CNAs, probably due to tumour heterogeneity and/or poor-quality DNA. Absence of CNAs in cfDNA correlates with remission although low mutant DNA fraction in cfDNA might have contributed to absent CNAs in the 2 patients with progressive cancer. The presence of cfDNA CNAs correlated with progression in one patient. Further sWGS results for the remaining cfDNA are to follow.

Learning points: 1. sWGS is cost-effective and easy-to-perform test.

2. sWGS can potentially be used to monitor the status of TC during follow up.