Evaluation of clonal origin of malignant mesothelioma

Sabahattin Comertpay, Sandra Pastorino, Mika Tanji, Rosanna Mezzapelle, Oriana Strianese, Andrea Napolitano, Francine Baumann, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Shreya Kanodia, Harvey I. Pass, Barbara L. Parsons, Haining Yang, Michele Carbone

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy. Methods and results: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM. Conclusions: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.

Original languageEnglish
Article number301
JournalJournal of Translational Medicine
Volume12
Issue number1
DOIs
Publication statusPublished - 4 Dec 2014

Fingerprint

Asbestos
Tumors
Mineral Fibers
Fibers
Biopsy
Alleles
Neoplasms
Assays
Tissue
X Chromosome Inactivation
Hematologic Neoplasms
Sarcoma
Inhalation
Malignant Mesothelioma
Clone Cells
Inflammation

Keywords

  • Carcinogenesis
  • Clonal origin
  • HUMARA assay
  • Malignant mesothelioma
  • Polyclonal tumors

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Comertpay, S., Pastorino, S., Tanji, M., Mezzapelle, R., Strianese, O., Napolitano, A., ... Carbone, M. (2014). Evaluation of clonal origin of malignant mesothelioma. Journal of Translational Medicine, 12(1), [301]. https://doi.org/10.1186/s12967-014-0301-3

Evaluation of clonal origin of malignant mesothelioma. / Comertpay, Sabahattin; Pastorino, Sandra; Tanji, Mika; Mezzapelle, Rosanna; Strianese, Oriana; Napolitano, Andrea; Baumann, Francine; Weigel, Tracey; Friedberg, Joseph; Sugarbaker, Paul; Krausz, Thomas; Wang, Ena; Powers, Amy; Gaudino, Giovanni; Kanodia, Shreya; Pass, Harvey I.; Parsons, Barbara L.; Yang, Haining; Carbone, Michele.

In: Journal of Translational Medicine, Vol. 12, No. 1, 301, 04.12.2014.

Research output: Contribution to journalArticle

Comertpay, S, Pastorino, S, Tanji, M, Mezzapelle, R, Strianese, O, Napolitano, A, Baumann, F, Weigel, T, Friedberg, J, Sugarbaker, P, Krausz, T, Wang, E, Powers, A, Gaudino, G, Kanodia, S, Pass, HI, Parsons, BL, Yang, H & Carbone, M 2014, 'Evaluation of clonal origin of malignant mesothelioma', Journal of Translational Medicine, vol. 12, no. 1, 301. https://doi.org/10.1186/s12967-014-0301-3
Comertpay S, Pastorino S, Tanji M, Mezzapelle R, Strianese O, Napolitano A et al. Evaluation of clonal origin of malignant mesothelioma. Journal of Translational Medicine. 2014 Dec 4;12(1). 301. https://doi.org/10.1186/s12967-014-0301-3
Comertpay, Sabahattin ; Pastorino, Sandra ; Tanji, Mika ; Mezzapelle, Rosanna ; Strianese, Oriana ; Napolitano, Andrea ; Baumann, Francine ; Weigel, Tracey ; Friedberg, Joseph ; Sugarbaker, Paul ; Krausz, Thomas ; Wang, Ena ; Powers, Amy ; Gaudino, Giovanni ; Kanodia, Shreya ; Pass, Harvey I. ; Parsons, Barbara L. ; Yang, Haining ; Carbone, Michele. / Evaluation of clonal origin of malignant mesothelioma. In: Journal of Translational Medicine. 2014 ; Vol. 12, No. 1.
@article{d31a21fd9d4c444b8fb6efd63abf1252,
title = "Evaluation of clonal origin of malignant mesothelioma",
abstract = "The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy. Methods and results: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM. Conclusions: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic {"}field effect{"} of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.",
keywords = "Carcinogenesis, Clonal origin, HUMARA assay, Malignant mesothelioma, Polyclonal tumors",
author = "Sabahattin Comertpay and Sandra Pastorino and Mika Tanji and Rosanna Mezzapelle and Oriana Strianese and Andrea Napolitano and Francine Baumann and Tracey Weigel and Joseph Friedberg and Paul Sugarbaker and Thomas Krausz and Ena Wang and Amy Powers and Giovanni Gaudino and Shreya Kanodia and Pass, {Harvey I.} and Parsons, {Barbara L.} and Haining Yang and Michele Carbone",
year = "2014",
month = "12",
day = "4",
doi = "10.1186/s12967-014-0301-3",
language = "English",
volume = "12",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Evaluation of clonal origin of malignant mesothelioma

AU - Comertpay, Sabahattin

AU - Pastorino, Sandra

AU - Tanji, Mika

AU - Mezzapelle, Rosanna

AU - Strianese, Oriana

AU - Napolitano, Andrea

AU - Baumann, Francine

AU - Weigel, Tracey

AU - Friedberg, Joseph

AU - Sugarbaker, Paul

AU - Krausz, Thomas

AU - Wang, Ena

AU - Powers, Amy

AU - Gaudino, Giovanni

AU - Kanodia, Shreya

AU - Pass, Harvey I.

AU - Parsons, Barbara L.

AU - Yang, Haining

AU - Carbone, Michele

PY - 2014/12/4

Y1 - 2014/12/4

N2 - The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy. Methods and results: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM. Conclusions: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.

AB - The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. This dogma arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas, which originate as monoclonal tumors. The possible clonal origin of malignant mesothelioma (MM) has not been investigated. Asbestos inhalation induces a chronic inflammatory response at sites of fiber deposition that may lead to malignant transformation after 30-50 years latency. As many mesothelial cells are simultaneously exposed to asbestos fibers and to asbestos-induced inflammation, it may be possible that more than one cell undergoes malignant transformation during the process that gives rise to MM, and result in a polyclonal malignancy. Methods and results: To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 16 biopsies from 14 women MM patients. Out of 16 samples, one was non-informative due to skewed Lyonization in its normal adjacent tissue. Fourteen out of the 15 informative samples revealed two electrophoretically distinct methylated HUMARA alleles, the Corrected Allele Ratio (CR) calculated on the allele peak areas indicating polyclonal origin MM. Conclusions: Our results show that MM originate as polyclonal tumors and suggest that the carcinogenic "field effect" of mineral fibers leads to several premalignant clones that give rise to these polyclonal malignancies.

KW - Carcinogenesis

KW - Clonal origin

KW - HUMARA assay

KW - Malignant mesothelioma

KW - Polyclonal tumors

UR - http://www.scopus.com/inward/record.url?scp=84924766219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924766219&partnerID=8YFLogxK

U2 - 10.1186/s12967-014-0301-3

DO - 10.1186/s12967-014-0301-3

M3 - Article

VL - 12

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 301

ER -