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A correction has been published: N Engl J Med 2005;353(15):1640.

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Volume 352:2406-2412 June 9, 2005 Number 23
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Independent Clonal Origins of Distinct Tumor Foci in Multifocal Papillary Thyroid Carcinoma
Trisha M. Shattuck, B.S., William H. Westra, M.D., Paul W. Ladenson, M.D., and Andrew Arnold, M.D.

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ABSTRACT

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.


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From the Center for Molecular Medicine and Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington (T.M.S., A.A.); the Department of Pathology, Johns Hopkins Medical Institutions, Baltimore (W.H.W.); and the Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore (P.W.L.).

Address reprint requests to Dr. Arnold at the Center for Molecular Medicine, University of Connecticut School of Medicine, 263 Farmington Ave., Farmington, CT 06030-3101, or at molecularmedicine{at}uchc.edu.

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Related Letters:

Multifocal Papillary Thyroid Carcinoma
Gemsenjäger E. W., Heitz P. U., Schweizer I., DeVries J. H., Ladenson P. W., Arnold A., Westra W. H.
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N Engl J Med 2005; 353:1067-1068, Sep 8, 2005. Correspondence

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