Identification of targetable lesions in anaplastic thyroid cancer by genome profiling

Naveen Ravi, Minjun Yang, Sigurdur Gretarsson, Caroline Jansson, Nektaria Mylona, Saskia R. Sydow, Eleanor L. Woodward, Lars Ekblad, Johan Wennerberg, Kajsa Paulsson

Research output: Contribution to journalArticlepeer-review


Anaplastic thyroid cancer (ATC) is a rare and extremely malignant tumor with no available cure. The genetic landscape of this malignancy has not yet been fully explored. In this study, we performed whole exome sequencing and the RNA-sequencing of fourteen cases of ATC to delineate copy number changes, fusion gene events, and somatic mutations. A high frequency of genomic amplifications was seen, including 29% of cases having amplification of CCNE1 and 9% of CDK6; these events may be targetable by cyclin dependent kinase (CDK) inhibition. Furthermore, 9% harbored amplification of TWIST1, which is also a potentially targetable lesion. A total of 21 fusion genes in five cases were seen, none of which were recurrent. Frequent mutations included TP53 (55%), the TERT promoter (36%), and ATM (27%). Analyses of mutational signatures showed an involvement of processes that are associated with normal aging, defective DNA mismatch repair, activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) activity, failure of DNA double-strand break repair, and tobacco exposure. Taken together, our results shed new light on the tumorigenesis of ATC and show that a relatively large proportion (36%) of ATCs harbor genetic events that make them candidates for novel therapeutic approaches. When considering that ATC today has a mortality rate of close to 100%, this is highly relevant from a clinical perspective.

Original languageEnglish
Article number402
Issue number3
Publication statusPublished - 2019 Mar 22

Subject classification (UKÄ)

  • Cancer and Oncology

Free keywords

  • Anaplastic thyroid cancer
  • CCNE1
  • Copy number alterations
  • Formalin-fixed paraffin embedded tissues
  • Fusion genes
  • RNA-sequencing
  • Somatic mutations
  • Whole exome sequencing


Dive into the research topics of 'Identification of targetable lesions in anaplastic thyroid cancer by genome profiling'. Together they form a unique fingerprint.

Cite this