Evaluation of clonal origin of malignant mesothelioma.

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

doi:10.1186/s12967-014-0301-3

Abstract

BackgroundThe 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 resultsTo 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0301-3) contains supplementary material, which is available to authorized users.

Highlights

Malignant mesothelioma (MM) is an aggressive cancer arising from the transformation of the mesothelial lining of the pleura, peritoneum and pericardium
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
We first performed the Human androgen receptor (HUMARA) assay on control samples (Figure 2)

Summary

Introduction

Malignant mesothelioma (MM) is an aggressive cancer arising from the transformation of the mesothelial lining of the pleura, peritoneum and pericardium. It is a lethal cancer affecting approximately 3,200 individuals each year in the US, most of them die within 1 year from diagnosis [1]. The hypothesis that most cancers are of monoclonal origin is often accepted as a fact in the scientific community. 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

Results

Conclusion