Clonal evolution analysis of paired anaplastic and well-differentiated thyroid carcinomas reveals shared common ancestor

Genes Chromosomes Cancer. 2018 Dec;57(12):645-652. doi: 10.1002/gcc.22678. Epub 2018 Sep 24.


Foci of papillary or follicular thyroid carcinoma are frequently noted in thyroidectomy specimens of anaplastic thyroid carcinoma (ATC). However, whether ATCs evolve from these co-existing well-differentiated thyroid carcinomas (WDTCs) has not been well-understood. To investigate the progression of ATC in patients with co-existing WDTCs, five ATC tumors with co-existing WDTCs and matching normal tissues were whole-exome sequenced. After mapping the somatic alteration landscape, evolutionary lineages were constructed by sub-clone analysis. Though each tumor harbored at least some unique private mutations, all five ATCs demonstrated numerous overlapping mutations with matched WDTCs. Clonal analysis further demonstrated that each ATC/WDTC pair shared a common ancestor, with some pairs diverging early in their evolution and others in which the ATC seems to arise directly from a sub-clone of the WDTC. Though the precise lineal relationship remains ambiguous, based on the genetic relationship, our study clearly suggests a shared origin of ATC and WDTC.

Keywords: anaplastic thyroid carcinoma; clonal evolution; exome sequencing; well-differentiated thyroid carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinogenesis
  • Cell Differentiation
  • Clonal Evolution*
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA, Neoplasm
  • Exome
  • Female
  • Humans
  • Male
  • Middle Aged
  • Sequence Analysis, DNA
  • Thyroid Carcinoma, Anaplastic / genetics*
  • Thyroid Carcinoma, Anaplastic / pathology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology


  • DNA, Neoplasm