Overexpression and promoter mutation of the TERT gene in malignant pleural mesothelioma

Autor: M.C. Copin, Françoise Galateau-Sallé, Jessica Zucman-Rossi, J-C Nault, Ilir Hysi, Paul Hofman, Anne Tallet, Pascal Andujar, Didier Jean, A Renier, F. Le Pimpec-Barthes, M-C Jaurand, Aurélie Cazes
Přispěvatelé: Génomique fonctionnelle des tumeurs solides (U674), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex Immuno-oncology, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Service de chirurgie cardiaque [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de Pathologie [CHU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Nice (CHU Nice), CHI Créteil, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Chirurgie Thoracique, Paris, This work was supported by funds and grants from INSERM, the University of Paris-Descartes, the French League against Cancer (Ligue Nationale Contre le Cancer, 'Carte d’Identité des Tumeurs' CIT1 and CIT2 programs and the Comité de l’Oise), and the Chancellerie des Universités de Paris (Legs POIX)., Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Jean, Didier
Jazyk: angličtina
Rok vydání: 2014
Předmět:
telomerase reverse transcriptase (TERT)
Cancer Research
Telomerase
Lung Neoplasms
Thoracic neoplasm
[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
medicine.disease_cause
Bioinformatics
0302 clinical medicine
Gene expression
CDKN2A Gene Inactivation
Promoter Regions
Genetic
Regulation of gene expression
0303 health sciences
telomere
MESH: Telomerase
MESH: Gene Expression Regulation
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
mesothelioma
[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
MESH: Mutation
MESH: Neoplastic
Pleural Neoplasms
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Biology
MESH: Pleural Neoplasms
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
MESH: Promoter Regions
Genetic
Genetics
medicine
Humans
Telomerase reverse transcriptase
RNA
Messenger
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Molecular Biology
030304 developmental biology
MESH: RNA
Messenger
MESH: Humans
MESH: Mesothelioma
Mesothelioma
Malignant
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
asbestos
Telomere
MESH: Lung Neoplasms
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Cancer cell
Cancer research
mutation
Carcinogenesis
Zdroj: Oncogene
Oncogene, Nature Publishing Group, 2014, 33 (28), pp.3748-3752. ⟨10.1038/onc.2013.351⟩
Oncogene, 2014, 33 (28), pp.3748-3752. ⟨10.1038/onc.2013.351⟩
ISSN: 0950-9232
1476-5594
DOI: 10.1038/onc.2013.351⟩
Popis: International audience; Malignant pleural mesothelioma (MPM) is a very aggressive tumor with no known curative treatment. Better knowledge of the molecular mechanisms of mesothelial carcinogenesis is required to develop new therapeutic strategies. MPM, like all cancer cells, needs to maintain telomere length to prevent senescence. Previous studies suggested that the telomere lengthening mechanism in MPM is based mainly on telomerase activity. For this reason, we focused on the key catalytic enzyme, TERT (telomerase reverse transcriptase), by analyzing its gene expression in MPM and by studying the mechanism underlying its upregulation. We used our large collection of MPM composed of 61 MPM in culture and 71 frozen MPM tumor samples. Evaluation of TERT mRNA expression by quantitative RT-PCR showed overexpression in MPM in culture compared with normal mesothelial cells, and in MPM tumor samples compared with normal pleura. We identified a 'hot spot' of mutations in the TERT gene core promoter in both MPM in culture and in MPM tumor samples with an overall frequency of 15%. Furthermore, data clearly identified mutation in the TERT promoter as a mechanism of TERT mRNA upregulation in MPM. In contrast, gene copy number amplification was not associated with TERT overexpression. Then, we analyzed the clinicopathological, etiological and genetic characteristics of MPM with mutations in the TERT promoter. TERT promoter mutations were more frequent in MPM with sarcomatoid histologic subtype (P
Databáze: OpenAIRE
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