Whole‐genome sequencing of synchronous thyroid carcinomas identifies aberrant DNA repair in thyroid cancer dedifferentiation

• DOI: 10.1002/path.5359
• Publication Date: 2019-10-17T12:17:56Z
• Authors: Johan O Paulsson; Samuel Backman; Na Wang; Adam Stenman; Joakim Crona; Jessada Thutkawko...; Mehran Ghaderi; Emma Tham; Peter Stålberg; Jan Zedenius; C Christofer Juhlin
• Keywords: Microsatellite Instability

Abstract The genetics underlying thyroid cancer dedifferentiation is only partly understood and has not yet been characterised using comprehensive pan‐genomic analyses. We investigated a unique case with synchronous follicular carcinoma (FTC), poorly differentiated (PDTC), anaplastic (ATC), as well regional lymph node metastases from the PDTC ATC single patient whole‐genome sequencing (WGS). FTC displayed mutations in CALR , RB1 MSH2 exhibited TP53 DROSHA APC TERT additional DNA repair genes – associated an immense increase sub‐clonal somatic mutations. All components overrepresentation of C>T transitions microsatellite instability (MSI) ATC, borderline MSI FTC. Clonality analyses pinpointed shared ancestral clone enriched for ‐associated regulation identified important sub‐clones each tumour component already present corresponding preceding lesion. This genomic characterisation natural progression reveals several novel interest future studies. Moreover, findings support theory stepwise process suggest that defects could play role clonal evolution cancer. © 2019 Pathological Society Great Britain Ireland. Published by John Wiley & Sons, Ltd.