Error-corrected next generation sequencing - Promises and challenges for genotoxicity and cancer risk assessment.
Mutat Res Rev Mutat Res
; 792: 108466, 2023.
Article
in En
| MEDLINE
| ID: mdl-37643677
ABSTRACT
Error-corrected Next Generation Sequencing (ecNGS) is rapidly emerging as a valuable, highly sensitive and accurate method for detecting and characterizing mutations in any cell type, tissue or organism from which DNA can be isolated. Recent mutagenicity and carcinogenicity studies have used ecNGS to quantify drug-/chemical-induced mutations and mutational spectra associated with cancer risk. ecNGS has potential applications in genotoxicity assessment as a new readout for traditional models, for mutagenesis studies in 3D organotypic cultures, and for detecting off-target effects of gene editing tools. Additionally, early data suggest that ecNGS can measure clonal expansion of mutations as a mechanism-agnostic early marker of carcinogenic potential and can evaluate mutational load directly in human biomonitoring studies. In this review, we discuss promising applications, challenges, limitations, and key data initiatives needed to enable regulatory testing and adoption of ecNGS - including for advancing safety assessment, augmenting weight-of-evidence for mutagenicity and carcinogenicity mechanisms, identifying early biomarkers of cancer risk, and managing human health risk from chemical exposures.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
High-Throughput Nucleotide Sequencing
/
Mutagens
Type of study:
Etiology_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Mutat Res Rev Mutat Res
Year:
2023
Type:
Article
Affiliation country:
Canada