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      Clinical utility of RASSF1A methylation in human malignancies

      1 , 1 , *

      British Journal of Cancer

      Nature Publishing Group

      RASSF1A, hippo pathway, gene methylation, cancer, biomaker

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          Abstract

          The high frequency of RASSF1A methylation has been noted in a vast number of patients in a broad spectrum of malignancies, suggesting that RASSF1A inactivation is associated with cancer pathogenesis. However, whether this recurrent incidence of RASSF1A hypermethylation in human malignancies and its association with more aggressive tumour phenotype is a frequent event across different cancer types has not yet been discussed. In this review, we interrogated existing evidence for association of RASSF1A hypermethylation with clinicopathological characteristics that can indicate more invasive lesions.

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          The fundamental role of epigenetic events in cancer.

          Patterns of DNA methylation and chromatin structure are profoundly altered in neoplasia and include genome-wide losses of, and regional gains in, DNA methylation. The recent explosion in our knowledge of how chromatin organization modulates gene transcription has further highlighted the importance of epigenetic mechanisms in the initiation and progression of human cancer. These epigenetic changes -- in particular, aberrant promoter hypermethylation that is associated with inappropriate gene silencing -- affect virtually every step in tumour progression. In this review, we discuss these epigenetic events and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.
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            Metastasis: a question of life or death.

            The metastatic process is highly inefficient--very few of the many cells that migrate from the primary tumour successfully colonize distant sites. One proposed mechanism to explain this inefficiency is provided by the cancer stem cell model, which hypothesizes that micrometastases can only be established by tumour stem cells, which are few in number. However, recent in vitro and in vivo observations indicate that apoptosis is an important process regulating metastasis. Here we stress that the inhibition of cell death, apart from its extensively described function in primary tumour development, is a crucial characteristic of metastatic cancer cells.
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              Gene expression profiling in breast cancer: classification, prognostication, and prediction.

              Microarray-based gene expression profiling has had a major effect on our understanding of breast cancer. Breast cancer is now perceived as a heterogeneous group of different diseases characterised by distinct molecular aberrations, rather than one disease with varying histological features and clinical behaviour. Gene expression profiling studies have shown that oestrogen-receptor (ER)-positive and ER-negative breast cancers are distinct diseases at the transcriptomic level, that additional molecular subtypes might exist within these groups, and that the prognosis of patients with ER-positive disease is largely determined by the expression of proliferation-related genes. On the basis of these principles, a molecular classification system and prognostic multigene classifiers based on microarrays or derivative technologies have been developed and are being tested in randomised clinical trials and incorporated into clinical practice. In this review, we focus on the conceptual effect and potential clinical use of the molecular classification of breast cancer, and discuss prognostic and predictive multigene predictors. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Affiliations
                [1 ]CRUK/MRC Oxford Institute, Department of Oncology, University of Oxford , Oxford, UK
                Author notes
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                28 July 2015
                09 July 2015
                : 113
                : 3
                : 372-381
                26158424 4522630 bjc2015221 10.1038/bjc.2015.221
                Copyright © 2015 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                Categories
                Review

                Oncology & Radiotherapy

                rassf1a, biomaker, cancer, gene methylation, hippo pathway

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