Next‐Generation Genotoxicology: Using Modern Sequencing Technologies to Assess Somatic Mutagenesis and Cancer Risk
Year: 2019
Type: review
Abstract: Mutations have a profound effect on human health, particularly through an increased risk of carcinogenesis and genetic disease. The strong correlation between mutagenesis and carcinogenesis has been a driving force behind genotoxicity research for more than 50 years. The stochastic and infrequent nature of mutagenesis makes it challenging to observe and to study. Indeed, decades have been spent developing increasingly sophisticated assays and methods to study these low-frequency genetic errors, in hopes of better predicting which chemicals may be carcinogens, understanding their mode of action, and informing guidelines to prevent undue human exposure. While effective, widely used genetic selection-based technologies have a number of limitations that have hampered major advancements in the field of genotoxicity. Emerging new tools, in the form of enhanced next-generation sequencing platforms and methods, are changing this paradigm. In this review, we discuss rapidly evolving sequencing tools and technologies, such as error-corrected sequencing and single cell analysis, which we anticipate will fundamentally reshape the field. In addition, we consider a variety emerging applications for these new technologies, including the detection of DNA adducts, inference of mutational processes based on genomic site and local sequence contexts, and evaluation of genome engineering fidelity, as well as other cutting-edge challenges for the next 50 years of environmental and molecular mutagenesis research. Environ. Mol. Mutagen. 61:135-151, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
DOI: 10.1002/em.22342
Authors: Jesse J. Salk, Scott R. Kennedy
Institutions: University of Washington, Seattle Foundation, Seagen (Canada)
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Awards: Developing High-Accuracy Sequencing Methods for Use in Early Cancer Detection, Disease Stratification, and Chemotherapy Resistance With Cell-Free DNA, Development of a Genotoxicity Assay using Duplex Sequencing, G4119534169, G5850682332, DEVELOPING HIGH-ACCURACY SEQUENCING METHODS FOR USE IN EARLY CANCER DETECTION, DISEASE STRATIFICATION, AND CHEMOTHERAPY RESISTANCE WITH CELL-FREE DNA, G8166743225, Developing SPLiT-Seq: A Massively Parallel Sequencing Method to Remove PCR Artifacts for Forensic STR Genotyping
OpenAlex ID: W2979587573