Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas

Ryan P. McCarthy, Mingsheng Wang, Timothy D. Jones, Randall W. Strate, Liang Cheng

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Purpose: Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors. Experimental Design: We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients. Results: Twenty of 22 (91%) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases. Conclusion: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.

Original languageEnglish
Pages (from-to)2414-2418
Number of pages5
JournalClinical Cancer Research
Volume12
Issue number8
DOIs
StatePublished - Apr 15 2006

Fingerprint

X Chromosome Inactivation
Loss of Heterozygosity
Neoplasms
Thyroidectomy
Microsatellite Repeats
Laser Capture Microdissection
Papillary Carcinoma
Papillary Thyroid cancer
Tumor Suppressor Genes
Thyroid Neoplasms
Paraffin
Formaldehyde
Research Design
Clone Cells
Chromosomes
Neoplasm Metastasis
DNA
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas. / McCarthy, Ryan P.; Wang, Mingsheng; Jones, Timothy D.; Strate, Randall W.; Cheng, Liang.

In: Clinical Cancer Research, Vol. 12, No. 8, 15.04.2006, p. 2414-2418.

Research output: Contribution to journalArticle

McCarthy, Ryan P. ; Wang, Mingsheng ; Jones, Timothy D. ; Strate, Randall W. ; Cheng, Liang. / Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 8. pp. 2414-2418.
@article{645885c9a1c94620a038e6a5337bc096,
title = "Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas",
abstract = "Purpose: Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors. Experimental Design: We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients. Results: Twenty of 22 (91{\%}) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87{\%}) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases. Conclusion: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.",
author = "McCarthy, {Ryan P.} and Mingsheng Wang and Jones, {Timothy D.} and Strate, {Randall W.} and Liang Cheng",
year = "2006",
month = "4",
day = "15",
doi = "10.1158/1078-0432.CCR-05-2818",
language = "English",
volume = "12",
pages = "2414--2418",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Molecular evidence for the same clonal origin of multifocal papillary thyroid carcinomas

AU - McCarthy, Ryan P.

AU - Wang, Mingsheng

AU - Jones, Timothy D.

AU - Strate, Randall W.

AU - Cheng, Liang

PY - 2006/4/15

Y1 - 2006/4/15

N2 - Purpose: Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors. Experimental Design: We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients. Results: Twenty of 22 (91%) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases. Conclusion: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.

AB - Purpose: Patients with papillary thyroid carcinoma often have two or more distinct papillary tumors at thyroidectomy. Whether these multifocal papillary lesions are clonally related or whether they arise independently is unknown as previous studies have shown conflicting results. Molecular analysis of microsatellite alterations and X-chromosome inactivation status in separate tumors from the same patient can be used to define the genetic relationships among the multiple coexisting tumors. Experimental Design: We examined 64 separate tumors from 22 female patients who underwent thyroidectomy for thyroid carcinoma. All patients had multiple and separate papillary carcinomas (range, two to six). Genomic DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-capture microdissection. Loss of heterozygosity assays for three microsatellite polymorphic markers for putative tumor suppressor genes on chromosomes 3p25 (D3S1597), 9p21 (D9S161), and 18p11.22-p11 (D18S53) were done. In addition, X-chromosome inactivation analysis was done on the tumors from all patients. Results: Twenty of 22 (91%) cases showed allelic loss in one or more of the papillary lesions in at least one of the three polymorphic markers analyzed. Concordant allelic loss patterns between coexisting papillary tumors were seen in 20 of 23 (87%) cases. A concordant pattern of nonrandom X-chromosome inactivation in the multiple coexisting papillary lesions was seen in all informative cases. Conclusion: Our data suggest that the multifocal tumors in patients with papillary thyroid carcinoma often arise from the same clone. Thus, intrathryoid metastasis may play an important role in the spread of papillary thyroid carcinoma, a finding that has important therapeutic, diagnostic, and prognostic implications.

UR - http://www.scopus.com/inward/record.url?scp=33646399142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646399142&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-05-2818

DO - 10.1158/1078-0432.CCR-05-2818

M3 - Article

VL - 12

SP - 2414

EP - 2418

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 8

ER -