A 'DNA replication' signature of progression and negative outcome in colorectal cancer
| Autor: | M-J, Pillaire, J, Selves, K, Gordien, P-A, Gourraud, P-A, Gouraud, C, Gentil, M, Danjoux, C, Do, V, Negre, A, Bieth, R, Guimbaud, D, Trouche, P, Pasero, M, Méchali, J-S, Hoffmann, C, Cazaux |
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| Přispěvatelé: | Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'histo-pathologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| Rok vydání: | 2009 |
| Předmět: |
DNA Replication
Cancer Research DNA polymerase DNA Polymerase Theta Cell Cycle Proteins DNA-Directed DNA Polymerase medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Molecular Biology Gene ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences biology DNA replication Cancer Nuclear Proteins Cell cycle medicine.disease Minichromosome Maintenance Complex Component 7 Prognosis 3. Good health DNA-Binding Proteins Gene Expression Regulation Neoplastic [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Tumor progression 030220 oncology & carcinogenesis Multigene Family Cancer research biology.protein Disease Progression Carcinogenesis Colorectal Neoplasms |
| Zdroj: | Oncogene Oncogene, Nature Publishing Group, 2010, 29 (6), pp.876-887. ⟨10.1038/onc.2009.378⟩ |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/onc.2009.378⟩ |
| Popis: | Colorectal cancer is one of the most frequent cancers worldwide. As the tumor-node-metastasis (TNM) staging classification does not allow to predict the survival of patients in many cases, additional prognostic factors are needed to better forecast their outcome. Genes involved in DNA replication may represent an underexplored source of such prognostic markers. Indeed, accidents during DNA replication can trigger 'replicative stress', one of the main features of cancer from earlier stages onward. In this study, we assessed the expression of 47 'DNA replication' genes in primary tumors and adjacent normal tissues from a homogeneous series of 74 patients. We found that genes coding for translesional (TLS) DNA polymerases, initiation of DNA replication, S-phase signaling and protection of replication forks were significantly deregulated in tumors. We also observed that the overexpression of either the MCM7 helicase or the TLS DNA polymerase POLQ (if also associated with a concomitant overexpression of firing genes) was significantly related to poor patient survival. Our data suggest the existence of a 'DNA replication signature' that might represent a source of new prognostic markers. Such a signature could help in understanding the molecular mechanisms underlying tumor progression in colorectal cancer patients. |
| Databáze: | OpenAIRE |
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