The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of ina...

Cell Death & Disease - m6A demethylase FTO drives pancreatic ductal adenocarcinoma tumorigenesis and metastasis through remodeling PFKM mediated glycolysis

Chromosomal instability (CIN) is a hallmark of cancer, and a primary cause of genetic heterogeneity in tumors. Depending on the degree of CIN and the affected tissue, CIN can promote or suppress tumor...

The use of mice for this study was approved by the Institutional Animal Care and Use Committee at Stanford University, protocol number 26696. KrasLSL-G12D/+ (RRID:IMSR_JAX:008179), p53flox/flox (RRID:IMSR_JAX008462), R26LSL-tdTomato (RRID:IMSR_JAX:007914) and H11LSL-Cas9 (RRID:IMSR_JAX:027632) mice have been previously described20,21,64,65. All mice were...

Covalently bound DNA adducts are mutation precursors that contribute to aging and diseases such as cancer. Accurate detection of adducts in the genome will shed light on tumorigenesis. Commonly used adduct detection methods, such as liquid chromatography-mass spectrometry, are unable to pinpoint exact genomic locations of adducts. Long-read nanopore sequencing is an approach with the potential to accurately detect multiple types of DNA adducts at single-nucleotide precision. In this study, we developed a novel statistical toolkit, IonStats, to profile DNA adducts in nanopore sequencing data. Using IonStats, we investigated the effects of four adduct-inducing genotoxic compounds (aristolochic acid II, cisplatin, melphalan, and mitomycin C) using nanopore sequencing. Compared to untreated controls, adducted samples exhibited both shared and compound-specific perturbations in base quality scores, ionic current profiles, and read interruptions. Our study shows that nanopore sequencing can be effectively employed to detect and characterize DNA adducts, paving the way for high-resolution, high-throughput profiling of DNA damage and the exposome.