Experimental identification of cancer driver alterations in the era of pan‐cancer genomics

Korenjak, Michael; Zavadil, Jiří

doi:10.1111/cas.14210

Cited by 17 publications

(12 citation statements)

References 68 publications

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“…We note that many chemicals in a mixture, such as tobacco smoke, induce similar type(s) of mutation, e.g., both ROS and B[a]P (a prototype PAH), give rise predominantly to G:C→T:A transversion [13,31,32,146,170,172,174]. Thus, it is a formidable challenge to tease out the contribution of each chemical to the induced mutation spectrum in cells/individuals exposed in vitro/in vivo to complex mixture of chemicals, such as tobacco smoke [12,14,31,32,171,175].…”

Section: Oxidative Damage To Dna: Connection With Smoking and Cancermentioning

confidence: 99%

Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer

Caliri

Tommasi

Besaratinia

2021

Mutation Research/Reviews in Mutation Research

311

139

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Smoking is a major risk factor for a variety of diseases, including cancer and immune-mediated inflammatory diseases. Tobacco smoke contains a mixture of chemicals, including a host of reactive oxygen-and nitrogen species (ROS and RNS), among others, that can damage cellular and sub-cellular targets, such as lipids, proteins, and nucleic acids. A growing body of evidence supports a key role for smoking-induced ROS and the resulting oxidative stress in inflammation and carcinogenesis. This comprehensive and up-to-date review covers four interrelated topics, including 'smoking', 'oxidative stress', 'inflammation', and 'cancer'. The review discusses each of the four topics, while exploring the intersections among the topics by highlighting the macromolecular damage attributable to ROS. Specifically, oxidative damage to macromolecular targets, such as lipid peroxidation, post-translational modification of proteins, and DNA adduction, as well as enzymatic and non-enzymatic antioxidant defense mechanisms, and the multi-faceted repair pathways of oxidized lesions are described. Also discussed are the biological consequences of oxidative damage to macromolecules if they evade the defense mechanisms and/or are not repaired properly or in time. Emphasis is placed on the genetic-and epigenetic alterations that may lead to transcriptional deregulation of functionally-important genes and disruption of regulatory elements. Smoking-associated oxidative stress also activates the inflammatory response pathway, which triggers a cascade of events of which ROS production is an initial yet indispensable step. The release of ROS at the site of damage and inflammation helps combat foreign pathogens and restores the injured tissue, while simultaneously increasing the burden of oxidative stress. This creates a vicious cycle in which smoking-related oxidative stress causes inflammation, which in turn, results in further generation of ROS, and potentially increased oxidative damage to macromolecular targets that may lead to cancer initiation and/or progression.

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Section: Oxidative Damage To Dna: Connection With Smoking and Cancermentioning

confidence: 99%

Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer

Caliri

Tommasi

Besaratinia

2021

Mutation Research/Reviews in Mutation Research

311

139

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“…Non-synonymous mutations were found in 371 genes across all MEFs and in 77 genes across all HFFs with a wide range of VAFs ( Figure 4 A & B ). To evaluate the early events driving barrier bypass and immortalization, genes with heterozygous mutations (VAF between 0.25 and 0.75) were compared to the most recent COSMIC cancer gene census 27–32 . The comparison revealed 8 mutated cancer census genes in MEFs, including, TP53’s mouse orthologue Trp53, and 9 mutated cancer census genes in HFFs.…”

Section: Resultsmentioning

confidence: 99%

DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer

Zhivagui¹,

Valenzuela²,

Yeh³

et al. 2021

Preprint

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Ultraviolet A light (UVA) is commonly emitted by nail polish dryers with recent reports suggesting that long-term use of UV-nail polish dryers may increase the risk for developing skin cancer. However, no experimental evaluation has been conducted to reveal the effect of radiation emitted by UV-nail polish dryers on mammalian cells. Here, we examine the pre-mutagenic and mutagenic changes imprinted on the genomes of human and murine primary cell models due to irradiation by a UV-nail dryer. Our findings demonstrate that radiation from UV-nail devices is cytotoxic and genotoxic. Importantly, high levels of reactive oxygen species were observed in all irradiated samples. Analysis of somatic mutations revealed a dose-dependent increase of C:G>A:T substitutions in irradiated samples with a pattern consistent to the one of COSMIC signature 18, a mutational signature attributed to reactive oxygen species. Examination of previously generated skin cancer genomics data revealed that signature 18 is ubiquitously present in melanoma and that it accounts for ~12% of the observed driver mutations. In summary, this study demonstrates that radiation emitted by UV-nail polish dryers can both damage DNA and can permanently imprint somatic mutations on the genomes of mammalian cells. These results have far reaching implications in regard to public health and to preventing skin cancer due to occupational- or consumer-based exposure to ultraviolet light from artificial sources.

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“…Rapidly accumulating data from large-scale cancer genomics studies, many studies have focused pan-cancer analysis to estimate the whole genome, frequently mutated genes and other common genomic characterization that are related to the occurrence and development of cancer (29)(30)(31)(32). In this study, we examine the specific role and underlying mechanisms of NAAA in a pan-cancer dataset.…”

Section: Introductionmentioning

confidence: 99%

Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

et al. 2022

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N-Acylethanolamine Acid Amidase (NAAA) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of NAAA was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

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Experimental identification of cancer driver alterations in the era of pan‐cancer genomics

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 17 publications

References 68 publications

Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer

Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer

DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer

Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer

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