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Translating cancer epigenomics into the clinic: focus on lung cancer

  • Author Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    Josep Mari-Alexandre
    Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    Affiliations
    Unit of Inherited Cardiovascular Diseases, Sudden Death and Mechanisms of Disease, Health Research Institute La Fe, Valencia, Spain
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  • Author Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    Angel Diaz-Lagares
    Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    Affiliations
    Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS), CIBERONC, Santiago de Compostela, Spain
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  • Author Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    Maria Villalba
    Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    Affiliations
    Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain

    CIBERONC, IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain
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  • Oscar Juan
    Affiliations
    Biomarkers and Precision Medicine Unit. Health Research Institute La Fe, Valencia, Spain
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  • Author Footnotes
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
    Ana B. Crujeiras
    Correspondence
    Ana B. Crujeiras, Molecular and Cellular Endocrinology Area, Health Research Institute of Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), C/ Choupana, s/n, 15706 Santiago de Compostela, Spain
    Footnotes
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
    Affiliations
    Laboratory of Molecular and Cellular Endocrinology, Health Research Institute of Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain

    CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Madrid, Spain
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  • Author Footnotes
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
    Alfonso Calvo
    Correspondence
    Alfonso Calvo, CIBERONC, IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Avda. Pío XII, 55. 31008 Pamplona, Navarra, Spain
    Footnotes
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
    Affiliations
    Department of Histology and Pathology, School of Medicine, University of Navarra, Pamplona, Navarra, Spain

    CIBERONC, IDISNA and Program in Solid Tumors and Biomarkers, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Navarra, Spain
    Search for articles by this author
  • Author Footnotes
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
    Juan Sandoval
    Correspondence
    Reprint requests: Juan Sandoval, 6th Floor, Biomarkers and Precision Medicine Unit. Health Research Institute La Fe, Avda. Fernando Abril Martorell 106, 46026 Valencia, Spain
    Footnotes
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
    Affiliations
    Biomarkers and Precision Medicine Unit. Health Research Institute La Fe, Valencia, Spain
    Search for articles by this author
  • Author Footnotes
    1 Josep Mari-Alexandre, Angel Diaz-Lagares and Maria Villalba contributed equally to this article and should be considered as co-first authors.
    2 Ana Belen Crujeiras, Alfonso Calvo, Juan Sandoval should be considered as co-last authors.
      Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients. Of particular relevance is the identification of epigenetic biomarkers in lung cancer, one of the most prevalent and deadly types of cancer. DNA methylation of SHOX2 and RASSF1A could be used as diagnostic markers to differentiate between normal and tumor samples. MicroRNA and long noncoding RNA signatures associated with lung cancer development or tobacco smoke have also been identified. In addition to the field of biomarkers, therapeutic approaches using DNA methylation and histone deacetylation inhibitors are being tested in clinical trials for several cancer types. Moreover, new DNA editing techniques based on zinc finger and CRISPR/Cas9 technologies allow specific modification of aberrant methylation found in oncogenes or tumor suppressor genes. We envision that epigenomics will translate into the clinical field and will have an impact on lung cancer diagnosis/prognosis and treatment.

      Abbreviations:

      BAL (bronchoalveolar lavage), ChIA-PET (chromatin interaction analysis with paired-end tag), ChIP-seq (chromatin inmunoprecipitation and massively parallel sequencing), circ-ncRNA (circulating noncoding RNA), CRC (colorectal cancer), CRISPR-Cas9 (clustered, regularly-interspaced short palindromic repeats-associated protein 9), CSC (cigarette smoke condensate), ddPCR (droplet digital PCR), DNMT (DNA methyltransferase), DNMTI (DNA methyltransferase inhibitor), EMT (epithelial-to-mesenchymal transition), HDAC (histone deacetylase), HDACI (histone deacetylase inhibitor), HMA (hypomethylation agents), HMT (histone methyltransferase), lncRNA (long noncoding RNA), miRNA (microRNA), MGMT (O-6-methylguanine-DNA methyltransferase), ncRNA (non-coding RNA), NGS (next generation sequencing), NSCLC (non-smallcell lung cancer), PAM (protospacer adjacent motif), PCa (prostate cancer), PTM (post-translational modifications), SCC (squamous cell carcinomas), SCLC (small-cell lung cancer), sncRNA (short noncoding RNA), THU (tetrahydrouridine), TSG (tumor supresor gene), VEGF-A (vascular endothelial growth factor A), ZFP (zinc finger proteins)
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