title: Evaluation of clonal origin of malignant mesothelioma.
abstract: BACKGROUND
  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.
  
  
  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.
authors.forename: Sabahattin
authors.initials: S
authors.lastname: Comertpay
authors.forename: Sandra
authors.initials: S
authors.lastname: Pastorino
authors.forename: Mika
authors.initials: M
authors.lastname: Tanji
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mezzapelle
authors.forename: Oriana
authors.initials: O
authors.lastname: Strianese
authors.forename: Andrea
authors.initials: A
authors.lastname: Napolitano
authors.forename: Francine
authors.initials: F
authors.lastname: Baumann
authors.forename: Tracey
authors.initials: T
authors.lastname: Weigel
authors.forename: Joseph
authors.initials: J
authors.lastname: Friedberg
authors.forename: Paul
authors.initials: P
authors.lastname: Sugarbaker
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Amy
authors.initials: A
authors.lastname: Powers
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudino
authors.forename: Shreya
authors.initials: S
authors.lastname: Kanodia
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Pass
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Parsons
authors.forename: Haining
authors.initials: H
authors.lastname: Yang
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, HI, USA. mcarbone@cc.hawaii.edu.
authors.forename: Michele
authors.initials: M
authors.lastname: Carbone
mesh_terms: D000368:Aged; D000483:Alleles; D005260:Female; D006801:Humans; D008654:Mesothelioma / Q000473:pathology*; D008875:Middle Aged; D011944:Receptors, Androgen / Q000235:genetics
chemical_list: D011944:Receptors, Androgen