GRCh38 · COSMIC v99


This section shows a summary for the selected study (COSU identifier) or publication (COSP identifier). Studies may have been performed by the Sanger Institute Cancer Genome Project, or imported from the ICGC/TCGA. You can see more information on the help pages.

Whole-genome sequencing of synchronous thyroid carcinomas identifies aberrant DNA repair in thyroid cancer dedifferentiation.
Paper ID
Paulsson JO, Backman S, Wang N, Stenman A, Crona J, Thutkawkorapin J, Ghaderi M, Tham E, Stålberg P, Zedenius J and Juhlin CC
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
The Journal of pathology, 2019
ISSN: 1096-9896
PMID: 31621921 (view at PubMed or Europe PMC)
The genetics underlying thyroid cancer dedifferentiation is only partly understood and has not yet been characterized using comprehensive pan-genomic analyses. We investigated a unique case with synchronous follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC), as well as regional lymph node metastases from the PDTC and ATC from a single patient using whole-genome sequencing (WGS). The FTC displayed mutations in CALR, RB1 and MSH2 and the PDTC exhibited mutations in TP53, DROSHA, APC, TERT and additional DNA repair genes - associated with an immense increase in subclonal somatic mutations. All components displayed an overrepresentation of C>T transitions with associated microsatellite instability (MSI) in the PDTC and ATC, with borderline MSI in the FTC. Clonality analyses pinpointed a shared ancestral clone enriched for mutations in TP53-associated regulation of DNA repair and identified important sub-clones for each tumour component already present in the corresponding preceding lesion. This genomic characterization of the natural progression of thyroid cancer reveals several novel genes of interest for future studies. Moreover, the findings support the theory of a stepwise dedifferentiation process and suggest that defects in DNA repair could play an important role in the clonal evolution of thyroid cancer. This article is protected by copyright. All rights reserved.
Paper Status