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    Radiation biology and oncology in the genomic era.

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    Authors
    Kerns, SL
    Chuang, KH
    Hall, W
    Werner, Z
    Chen, Y
    Ostrer, H
    West, Catharine ML
    Rosenstein, B
    Affiliation
    Department of Radiation Oncology, University of Rochester Medical Center , Rochester, NY
    Issue Date
    2018
    
    Metadata
    Show full item record
    Abstract
    Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side effects. An individual's radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects. Current thinking is that some will be tissue specific, and future tests will be tailored to the normal tissues at risk. The relationship between normal and tumor cell radiosensitivity is poorly understood. Data are emerging suggesting interplay between germline genetic variation and epigenetic modification with growing evidence that changes in DNA methylation regulate the radiosensitivity of cancer cells and histone acetyltransferase inhibitors have radiosensitizing effects. Changes in histone methylation can also impair DNA damage response signaling and alter radiosensitivity. An important effort to advance radiobiology in the genomic era was establishment of the Radiogenomics Consortium to enable the creation of the large radiotherapy cohorts required to exploit advances in genomics. To address challenges in harmonizing data from multiple cohorts, the consortium established the REQUITE project to collect standardized data and genotyping for ~5,000 patients. The collection of detailed dosimetric data is important to produce validated multivariable models. Continued efforts will identify new genes that impact on radiosensitivity to generate new knowledge on toxicity pathogenesis and tests to incorporate into the clinical decision-making process.
    Citation
    Kerns SL, Chuang KH, Hall W, Werner Z, Chen Y, Ostrer H, et al. Radiation biology and oncology in the genomic era. Br J Radiol. 2018 Nov;91(1091):20170949.
    Journal
    The British Journal of Radiology
    URI
    http://hdl.handle.net/10541/621396
    DOI
    10.1259/bjr.20170949
    PubMed ID
    29888979
    Additional Links
    https://dx.doi.org/10.1259/bjr.20170949
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1259/bjr.20170949
    Scopus Count
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