Faculty Collaboration Database

Radiation biology and oncology in the genomic era. Br J Radiol 2018 Nov;91(1091):20170949

Date

06/12/2018

Pubmed ID

29888979

Pubmed Central ID

PMC6475928

DOI

10.1259/bjr.20170949

Scopus ID

2-s2.0-85053833312 (requires institutional sign-in at Scopus site)   25 Citations

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.

Author List

Kerns SL, Chuang KH, Hall W, Werner Z, Chen Y, Ostrer H, West C, Rosenstein B

Authors

William Adrian Hall MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin
Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylation
Cytokines
DNA Methylation
Epigenesis, Genetic
Forecasting
Genetic Markers
Genomics
Histone Acetyltransferases
Humans
Medical Oncology
Methylation
Neoplasms
Precision Medicine
Radiation Tolerance
Radiobiology
Tumor Microenvironment