title: Syntenic relationships between genomic profiles of fiber-induced murine and human malignant mesothelioma.
abstract: Malignant mesothelioma (MM) is an aggressive tumor with a poor prognosis mainly linked to past asbestos exposure. Murine models of MM based on fiber exposure have been developed to elucidate the mechanism of mesothelioma formation. Genomic alterations in murine MM have now been partially characterized. To gain insight into the pathophysiology of mesothelioma, 16 murine and 35 human mesotheliomas were characterized by array-comparative genomic hybridization and were screened for common genomic alterations. Alteration of the 9p21 human region, often by biallelic deletion, was the most frequent alteration in both species, in agreement with the CDKN2A/CDKN2B locus deletion in human disease and murine models. Other shared aberrations were losses of 1p36.3-p35 and 13q14-q33 and gains of 5p15.3-p13 regions. However, some differences were noted, such as absence of recurrent alterations in mouse regions corresponding to human chromosome 22. Comparison between altered recurrent regions in asbestos-exposed and non-asbestos-exposed patients showed a significant difference in the 14q11.2-q21 region, which was also lost in fiber-induced murine mesothelioma. A correlation was also demonstrated between genomic instability and tumorigenicity of human mesothelioma xenografts in nude mice. Overall, these data show similarities between murine and human disease, and contribute to the understanding of the influence of fibers in the pathogenesis of mesothelioma and validation of the murine model for preclinical testing.
authors.affiliation: INSERM, U674, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Jean
authors.forename: Emilie
authors.initials: E
authors.lastname: Thomas
authors.forename: Elodie
authors.initials: E
authors.lastname: Manié
authors.forename: Annie
authors.initials: A
authors.lastname: Renier
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reynies
authors.forename: Céline
authors.initials: C
authors.lastname: Lecomte
authors.forename: Pascal
authors.initials: P
authors.lastname: Andujar
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Fleury-Feith
authors.forename: Françoise
authors.initials: F
authors.lastname: Galateau-Sallé
authors.forename: Marco
authors.initials: M
authors.lastname: Giovannini
authors.forename: Jessica
authors.initials: J
authors.lastname: Zucman-Rossi
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Jaurand
mesh_terms: D000368:Aged; D000483:Alleles; D000818:Animals; D001194:Asbestos / Q000009:adverse effects*; D002877:Chromosomes, Human / Q000235:genetics; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D016678:Genome / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics; D023281:Genomics; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010997:Pleural Neoplasms / Q000235:genetics* / Q000473:pathology; D026801:Synteny / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001194:Asbestos