Applying shallow whole genome sequencing to decipher genomic signatures in thyroid cancer - insight from a case study

Jumaah i Al; Miles Levy; Rebecca Allsopp; Karen Page; Shaw Jacqueline A; Narendra Reddy; Shailesh Gohil

doi:10.1530/endoabs.109.P91

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Endocrine Abstracts (2025) 109 P91 | DOI: 10.1530/endoabs.109.P91

SFEBES2025 Poster Presentations Endocrine Cancer and Late Effects (9 abstracts)

Applying shallow whole genome sequencing to decipher genomic signatures in thyroid cancer – insight from a case study

Ali Al Jumaah ^1,2 , Miles Levy ^1,2 , Rebecca Allsopp ¹ , Karen Page ¹ , Jacqueline A Shaw ¹ , Narendra Reddy ^1,2 & Shailesh Gohil ^1,2

Author affiliations

¹University of Leicester, Leicester, United Kingdom; ²University Hospitals of Leicester NHS Trust, Leicester, United Kingdom

Shallow Whole Genome Sequencing (sWGS) can detect Copy Number Alterations (CNAs) across the entire genome. It is more affordable than other DNA sequencing techniques and requires low DNA input. sWGS of circulating cell free DNA (cfDNA) has shown promising results in the surveillance of various carcinomas. However, little is known regarding its utility in thyroid carcinoma (TC). In this study, we investigated sWGS as a surveillance tool in a patient with follicular TC (FTC).

Aims and Objectives: Explore concordance of CNAs identified between tumour DNA and plasma cfDNA. Compare Tumour Fraction (TF) between longitudinally collected cfDNA samples. Interpret changes in TF against thyroglobulin levels and clinical imaging.

Case History: A 71-year-old patient was under FTC surveillance after undergoing total thyroidectomy and radioiodine. Tumour DNA was extracted from Formalin-Fixed Paraffin-Embedded (FFPE) tumour blocks using GeneRead™ DNA FFPE kit. cfDNA was extracted from 2 plasma samples collected over 6 months using the QIAMP^® circulating nucleic acid kit. sWGS was performed using the Ion RepoSeqPGS™ platform. Thyroglobulin and clinical imaging were assessed at intervals dictated by oncology follow-up.

Results: sWGS showed matching CNA pattern of tumour DNA and cfDNA in the first plasma sample at 42% TF. Thyroglobulin was detectable at 109.7μg/l. Imaging showed probable intraparotid lymph node metastases. Detectable plasma CNAs and thyroglobulin fits with this clinic picture. Second plasma sample is awaiting analysis. Between plasma samples, CT imaging showed new bone metastases with rising thyroglobulin and the patient unfortunately died shortly after second sample collection.

Discussion: Matching CNAs between primary tumour DNA and cfDNA are detectable in in this case using sWGS and it would be interesting to see if TF increases in line with tumour progression in the second sample. sWGS is a low-cost DNA sequencing technique and further research is warranted to support its role in surveillance of TC.