Mutational signatures: emerging concepts, caveats and clinical applications

G Koh, A Degasperi, X Zou, S Momen… - Nature Reviews …, 2021 - nature.com
Whole-genome sequencing has brought the cancer genomics community into new territory.
Thanks to the sheer power provided by the thousands of mutations present in each patient's …

Therapeutic and prognostic insights from the analysis of cancer mutational signatures

SW Brady, AM Gout, J Zhang - Trends in Genetics, 2022 - cell.com
The somatic mutations in each cancer genome are caused by multiple mutational
processes, each of which leaves a characteristic imprint (or 'signature'), potentially caused …

Enhanced prime editing systems by manipulating cellular determinants of editing outcomes

PJ Chen, JA Hussmann, J Yan, F Knipping… - Cell, 2021 - cell.com
While prime editing enables precise sequence changes in DNA, cellular determinants of
prime editing remain poorly understood. Using pooled CRISPRi screens, we discovered that …

Substitution mutational signatures in whole-genome–sequenced cancers in the UK population

A Degasperi, X Zou, T Dias Amarante… - Science, 2022 - science.org
Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses,
revealing mutational signatures, imprints of DNA damage, and repair processes that have …

Prime editing efficiency and fidelity are enhanced in the absence of mismatch repair

J Ferreira da Silva, GP Oliveira, EA Arasa-Verge… - Nature …, 2022 - nature.com
Prime editing (PE) is a powerful genome engineering approach that enables the introduction
of base substitutions, insertions and deletions into any given genomic locus. However, the …

Somatic mutation rates scale with lifespan across mammals

A Cagan, A Baez-Ortega, N Brzozowska, F Abascal… - Nature, 2022 - nature.com
The rates and patterns of somatic mutation in normal tissues are largely unknown outside of
humans,,,,,–. Comparative analyses can shed light on the diversity of mutagenesis across …

The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells

GCC Koh, S Boushaki, SJ Zhao, AM Pregnall… - Nature Genetics, 2024 - nature.com
The chemotherapeutic agent CX-5461, or pidnarulex, has been fast-tracked by the United
States Food and Drug Administration for early-stage clinical studies of BRCA1-, BRCA2-and …

Somatic evolution of marine transmissible leukemias in the common cockle, Cerastoderma edule

AL Bruzos, M Santamarina, D Garcia-Souto, S Díaz… - Nature Cancer, 2023 - nature.com
Transmissible cancers are malignant cell lineages that spread clonally between individuals.
Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like …

The evolution of two transmissible cancers in Tasmanian devils

MR Stammnitz, K Gori, YM Kwon, E Harry, FJ Martin… - Science, 2023 - science.org
Tasmanian devils have spawned two transmissible cancer lineages, named devil facial
tumor 1 (DFT1) and devil facial tumor 2 (DFT2). We investigated the genetic diversity and …

Inherited MUTYH mutations cause elevated somatic mutation rates and distinctive mutational signatures in normal human cells

PS Robinson, LE Thomas, F Abascal, H Jung… - Nature …, 2022 - nature.com
Cellular DNA damage caused by reactive oxygen species is repaired by the base excision
repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic …