Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma

N Engl J Med. 2005 Jun 9;352(23):2406-12. doi: 10.1056/NEJMoa044190.


Background: Papillary thyroid carcinoma is frequently multifocal. We investigated whether noncontiguous tumor foci arise from intraglandular metastases from a single primary tumor or originate as unrelated clones derived from independent precursors.

Methods: Using a polymerase-chain-reaction assay involving the human androgen receptor gene (HUMARA), we analyzed the patterns of X-chromosome inactivation of multiple distinct foci of well-differentiated multifocal papillary thyroid cancer from 17 women.

Results: Multiple thyroid tumor foci from 10 of 17 patients yielded DNA of adequate quality and were heterozygous for the HUMARA polymorphism and hence suitable for analysis. A single X chromosome was inactivated in each focus, consistent with its monoclonality. When the specific monoclonal configurations of each patient's discrete tumor foci were compared, discordant patterns indicative of independent origins were observed among the tumors from five patients; results in the remaining five were consistent with either a shared or independent clonal origin.

Conclusions: Individual tumor foci in patients with multifocal papillary thyroid cancer often arise as independent tumors.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Chromosomes, Human, X / genetics
  • Clone Cells
  • DNA, Neoplasm / analysis*
  • Dosage Compensation, Genetic*
  • Female
  • Heterozygote
  • Humans
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / pathology
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Receptors, Androgen / genetics
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology


  • AR protein, human
  • DNA, Neoplasm
  • Receptors, Androgen