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      Minichromosome Maintenance (MCM) Family as potential diagnostic and prognostic tumor markers for human gliomas

      research-article
      1 , 1 , 1 , 1 , 2 ,
      BMC Cancer
      BioMed Central
      Glioma, MCMs, Tumor marker, Prognosis

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          Abstract

          Background

          Gliomas are the most common type of all central nervous system tumors. Almost all patients diagnosed with these tumors have a poor prognostic outcome. We aimed to identify novel glioma prognosis-associated candidate genes.

          Methods

          We applied WebArrayDB software to span platform integrate and analyze the microarray datasets. We focused on a subset of the significantly up-regulated genes, the minichromosome maintenance (MCM) family. We used frozen glioma samples to predict the relationship between the expression of MCMs and patients outcome by qPCR and western blot.

          Results

          We found that MCMs expression was significantly up-regulated in glioma samples. MCM2-7 and MCM10 expressions were associated with WHO tumor grade. High MCM2 mRNA expression appeared to be strongly associated with poor overall survival in patients with high grade glioma. Furthermore, we report that MCM7 is strongly correlated with patient outcome in patients with WHO grade II-IV tumor. MCM3 expression was found to be up-regulated in glioma and correlated with overall survival in patients with WHO grade III tumor. MCM2, MCM3 and MCM7 expression levels were of greater prognostic relevance than histological diagnosis according to the current WHO classification system.

          Conclusions

          High expression of MCM 2, MCM3 and MCM7 mRNA correlated with poor outcome and may be clinically useful molecular prognostic markers in glioma.

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          Most cited references51

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          DNA replication in eukaryotic cells.

          The maintenance of the eukaryotic genome requires precisely coordinated replication of the entire genome each time a cell divides. To achieve this coordination, eukaryotic cells use an ordered series of steps to form several key protein assemblies at origins of replication. Recent studies have identified many of the protein components of these complexes and the time during the cell cycle they assemble at the origin. Interestingly, despite distinct differences in origin structure, the identity and order of assembly of eukaryotic replication factors is highly conserved across all species. This review describes our current understanding of these events and how they are coordinated with cell cycle progression. We focus on bringing together the results from different organisms to provide a coherent model of the events of initiation. We emphasize recent progress in determining the function of the different replication factors once they have been assembled at the origin.
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            Brain tumors.

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              MCM proteins in DNA replication.

              B Tye (1998)
              The MCM proteins are essential replication initiation factors originally identified as proteins required for minichromosome maintenance in Saccharomyces cerevisiae. The best known among them are a family of six structurally related proteins, MCM2-7, which are evolutionally conserved in all eukaryotes. The MCM2-7 proteins form a hexameric complex. This complex is a key component of the prereplication complex that assembles at replication origins during early G1 phase. New evidence suggests that the MCM2-7 proteins may be involved not only in the initiation but also in the elongation of DNA replication. Orchestration of the functional interactions between the MCM2-7 proteins and other components of the prereplication complex by cell cycle-dependent protein kinases results in initiation of DNA synthesis once every cell cycle.
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                Author and article information

                Contributors
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central
                1471-2407
                2014
                21 July 2014
                : 14
                : 526
                Affiliations
                [1 ]Department of Neurosurgery of the First Clinical Hospital, Jilin University, 71 Xinmin St, Changchun, Jilin 130021, China
                [2 ]Department of Pathology and Laboratory Medicine, University of California, Irvine, USA
                Article
                1471-2407-14-526
                10.1186/1471-2407-14-526
                4223428
                25046975
                f97d2332-7a35-474d-bc2b-bb112aef0058
                Copyright © 2014 Hua et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 May 2014
                : 15 July 2014
                Categories
                Research Article

                Oncology & Radiotherapy
                glioma,mcms,tumor marker,prognosis
                Oncology & Radiotherapy
                glioma, mcms, tumor marker, prognosis

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