Evidence for common clonal origin of multifocal lung cancers

Xiaoyan Wang, Mingsheng Wang, Gregory T. MacLennan, Fadi W. Abdul-Karim, John Eble, Timothy D. Jones, Felix Olobatuyi, Rosana Eisenberg, Oscar Cummings, Shaobo Zhang, Antonio Lopez-Beltran, Rodolfo Montironi, Suqin Zheng, Haiqun Lin, Darrell Davidson, Liang Cheng

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Background Lung cancer is the most common cause of cancer death in the United States. Multiple anatomically separate but histologically similar lung tumors are often found in the same patient. The clonal origin of multiple lung tumors is uncertain. Methods We analyzed 70 lung tumors from 30 patients (23 females and seven males) who underwent surgical resection for lung epithelial tumors, of whom 26 had non-small cell carcinomas and four had carcinoid/atypical carcinoid tumors. All patients had multiple tumors (two to five) involving one or both lungs. Genomic DNA was extracted from paraffin-embedded tissue sections using laser capture microdissection and analyzed for loss of heterozygosity, TP53 mutations, and X-chromosome inactivation status. The percentage (95% confidence interval [CI]) of patients in whom there were concordant patterns of genetic alteration was calculated. Results All 30 case subjects showed loss of heterozygosity (LOH) in at least one and at most four of the six polymorphic microsatellite markers. Completely concordant LOH patterns between synchronous and metachronous cancers in individual patients were seen in 26 (87%) of 30 informative patients (95% CI = 75% to 99%). Identical point mutations were present in eight of 10 patients who exhibited TP53 mutation by sequencing. Tumors in 18 (78%) of 23 female patients (95% CI = 67% to 98%) showed identical X-chromosome inactivation patterns. Combining the results of LOH studies, TP53 mutation screening analyses, and X-chromosome inactivation data, we demonstrated that the multiple separate tumors in 23 (77%) of 30 patients (95% CI = 62% to 92%) had identical genetic changes, consistent with monoclonal origin of the separate tumors.ConclusionsOur data indicate that the great majority of multifocal lung cancers have a common clonal origin and that multifocality in lung cancer represents local and regional intrapulmonary metastasis.

Original languageEnglish
Pages (from-to)560-570
Number of pages11
JournalJournal of the National Cancer Institute
Volume101
Issue number8
DOIs
StatePublished - Apr 2009

Fingerprint

Lung Neoplasms
Loss of Heterozygosity
Neoplasms
X Chromosome Inactivation
Lung
Confidence Intervals
Carcinoid Tumor
Mutation
Laser Capture Microdissection
Point Mutation
Paraffin
Microsatellite Repeats
Cause of Death
Neoplasm Metastasis
Carcinoma
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evidence for common clonal origin of multifocal lung cancers. / Wang, Xiaoyan; Wang, Mingsheng; MacLennan, Gregory T.; Abdul-Karim, Fadi W.; Eble, John; Jones, Timothy D.; Olobatuyi, Felix; Eisenberg, Rosana; Cummings, Oscar; Zhang, Shaobo; Lopez-Beltran, Antonio; Montironi, Rodolfo; Zheng, Suqin; Lin, Haiqun; Davidson, Darrell; Cheng, Liang.

In: Journal of the National Cancer Institute, Vol. 101, No. 8, 04.2009, p. 560-570.

Research output: Contribution to journalArticle

Wang, X, Wang, M, MacLennan, GT, Abdul-Karim, FW, Eble, J, Jones, TD, Olobatuyi, F, Eisenberg, R, Cummings, O, Zhang, S, Lopez-Beltran, A, Montironi, R, Zheng, S, Lin, H, Davidson, D & Cheng, L 2009, 'Evidence for common clonal origin of multifocal lung cancers', Journal of the National Cancer Institute, vol. 101, no. 8, pp. 560-570. https://doi.org/10.1093/jnci/djp054
Wang, Xiaoyan ; Wang, Mingsheng ; MacLennan, Gregory T. ; Abdul-Karim, Fadi W. ; Eble, John ; Jones, Timothy D. ; Olobatuyi, Felix ; Eisenberg, Rosana ; Cummings, Oscar ; Zhang, Shaobo ; Lopez-Beltran, Antonio ; Montironi, Rodolfo ; Zheng, Suqin ; Lin, Haiqun ; Davidson, Darrell ; Cheng, Liang. / Evidence for common clonal origin of multifocal lung cancers. In: Journal of the National Cancer Institute. 2009 ; Vol. 101, No. 8. pp. 560-570.
@article{e2b8be1e97fc445dbc521ce223f95304,
title = "Evidence for common clonal origin of multifocal lung cancers",
abstract = "Background Lung cancer is the most common cause of cancer death in the United States. Multiple anatomically separate but histologically similar lung tumors are often found in the same patient. The clonal origin of multiple lung tumors is uncertain. Methods We analyzed 70 lung tumors from 30 patients (23 females and seven males) who underwent surgical resection for lung epithelial tumors, of whom 26 had non-small cell carcinomas and four had carcinoid/atypical carcinoid tumors. All patients had multiple tumors (two to five) involving one or both lungs. Genomic DNA was extracted from paraffin-embedded tissue sections using laser capture microdissection and analyzed for loss of heterozygosity, TP53 mutations, and X-chromosome inactivation status. The percentage (95{\%} confidence interval [CI]) of patients in whom there were concordant patterns of genetic alteration was calculated. Results All 30 case subjects showed loss of heterozygosity (LOH) in at least one and at most four of the six polymorphic microsatellite markers. Completely concordant LOH patterns between synchronous and metachronous cancers in individual patients were seen in 26 (87{\%}) of 30 informative patients (95{\%} CI = 75{\%} to 99{\%}). Identical point mutations were present in eight of 10 patients who exhibited TP53 mutation by sequencing. Tumors in 18 (78{\%}) of 23 female patients (95{\%} CI = 67{\%} to 98{\%}) showed identical X-chromosome inactivation patterns. Combining the results of LOH studies, TP53 mutation screening analyses, and X-chromosome inactivation data, we demonstrated that the multiple separate tumors in 23 (77{\%}) of 30 patients (95{\%} CI = 62{\%} to 92{\%}) had identical genetic changes, consistent with monoclonal origin of the separate tumors.ConclusionsOur data indicate that the great majority of multifocal lung cancers have a common clonal origin and that multifocality in lung cancer represents local and regional intrapulmonary metastasis.",
author = "Xiaoyan Wang and Mingsheng Wang and MacLennan, {Gregory T.} and Abdul-Karim, {Fadi W.} and John Eble and Jones, {Timothy D.} and Felix Olobatuyi and Rosana Eisenberg and Oscar Cummings and Shaobo Zhang and Antonio Lopez-Beltran and Rodolfo Montironi and Suqin Zheng and Haiqun Lin and Darrell Davidson and Liang Cheng",
year = "2009",
month = "4",
doi = "10.1093/jnci/djp054",
language = "English",
volume = "101",
pages = "560--570",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Evidence for common clonal origin of multifocal lung cancers

AU - Wang, Xiaoyan

AU - Wang, Mingsheng

AU - MacLennan, Gregory T.

AU - Abdul-Karim, Fadi W.

AU - Eble, John

AU - Jones, Timothy D.

AU - Olobatuyi, Felix

AU - Eisenberg, Rosana

AU - Cummings, Oscar

AU - Zhang, Shaobo

AU - Lopez-Beltran, Antonio

AU - Montironi, Rodolfo

AU - Zheng, Suqin

AU - Lin, Haiqun

AU - Davidson, Darrell

AU - Cheng, Liang

PY - 2009/4

Y1 - 2009/4

N2 - Background Lung cancer is the most common cause of cancer death in the United States. Multiple anatomically separate but histologically similar lung tumors are often found in the same patient. The clonal origin of multiple lung tumors is uncertain. Methods We analyzed 70 lung tumors from 30 patients (23 females and seven males) who underwent surgical resection for lung epithelial tumors, of whom 26 had non-small cell carcinomas and four had carcinoid/atypical carcinoid tumors. All patients had multiple tumors (two to five) involving one or both lungs. Genomic DNA was extracted from paraffin-embedded tissue sections using laser capture microdissection and analyzed for loss of heterozygosity, TP53 mutations, and X-chromosome inactivation status. The percentage (95% confidence interval [CI]) of patients in whom there were concordant patterns of genetic alteration was calculated. Results All 30 case subjects showed loss of heterozygosity (LOH) in at least one and at most four of the six polymorphic microsatellite markers. Completely concordant LOH patterns between synchronous and metachronous cancers in individual patients were seen in 26 (87%) of 30 informative patients (95% CI = 75% to 99%). Identical point mutations were present in eight of 10 patients who exhibited TP53 mutation by sequencing. Tumors in 18 (78%) of 23 female patients (95% CI = 67% to 98%) showed identical X-chromosome inactivation patterns. Combining the results of LOH studies, TP53 mutation screening analyses, and X-chromosome inactivation data, we demonstrated that the multiple separate tumors in 23 (77%) of 30 patients (95% CI = 62% to 92%) had identical genetic changes, consistent with monoclonal origin of the separate tumors.ConclusionsOur data indicate that the great majority of multifocal lung cancers have a common clonal origin and that multifocality in lung cancer represents local and regional intrapulmonary metastasis.

AB - Background Lung cancer is the most common cause of cancer death in the United States. Multiple anatomically separate but histologically similar lung tumors are often found in the same patient. The clonal origin of multiple lung tumors is uncertain. Methods We analyzed 70 lung tumors from 30 patients (23 females and seven males) who underwent surgical resection for lung epithelial tumors, of whom 26 had non-small cell carcinomas and four had carcinoid/atypical carcinoid tumors. All patients had multiple tumors (two to five) involving one or both lungs. Genomic DNA was extracted from paraffin-embedded tissue sections using laser capture microdissection and analyzed for loss of heterozygosity, TP53 mutations, and X-chromosome inactivation status. The percentage (95% confidence interval [CI]) of patients in whom there were concordant patterns of genetic alteration was calculated. Results All 30 case subjects showed loss of heterozygosity (LOH) in at least one and at most four of the six polymorphic microsatellite markers. Completely concordant LOH patterns between synchronous and metachronous cancers in individual patients were seen in 26 (87%) of 30 informative patients (95% CI = 75% to 99%). Identical point mutations were present in eight of 10 patients who exhibited TP53 mutation by sequencing. Tumors in 18 (78%) of 23 female patients (95% CI = 67% to 98%) showed identical X-chromosome inactivation patterns. Combining the results of LOH studies, TP53 mutation screening analyses, and X-chromosome inactivation data, we demonstrated that the multiple separate tumors in 23 (77%) of 30 patients (95% CI = 62% to 92%) had identical genetic changes, consistent with monoclonal origin of the separate tumors.ConclusionsOur data indicate that the great majority of multifocal lung cancers have a common clonal origin and that multifocality in lung cancer represents local and regional intrapulmonary metastasis.

UR - http://www.scopus.com/inward/record.url?scp=64749102206&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=64749102206&partnerID=8YFLogxK

U2 - 10.1093/jnci/djp054

DO - 10.1093/jnci/djp054

M3 - Article

C2 - 19351924

AN - SCOPUS:64749102206

VL - 101

SP - 560

EP - 570

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 8

ER -