Mutation Research-Reviews in Mutation Research最新文献

{"title":"From pathology to therapy: A comprehensive review of ATRX mutation related molecular functions and disorders","authors":"Fan Xu ,&nbsp;Daohan Yu ,&nbsp;Jiazheng Guo ,&nbsp;Jingze Hu ,&nbsp;Yunlei Zhao ,&nbsp;Chuanlu Jiang ,&nbsp;Xiangqi Meng ,&nbsp;Jinquan Cai ,&nbsp;Yan Zhao","doi":"10.1016/j.mrrev.2025.108537","DOIUrl":"10.1016/j.mrrev.2025.108537","url":null,"abstract":"<div><div>ATRX (alpha-thalassemia/mental retardation, X-linked), a chromatin remodeler, is one of the most commonly mutated genes in human cancer. The ATRX protein functions as a histone chaperone, facilitating the proper folding and assembly of histone proteins into nucleosome cores. Investigations into its molecular mechanisms have significantly advanced our understanding of its roles in diseases associated with chromosomal instability and defective DNA repair. In this comprehensive review, we delineate ATRX's critical function in maintaining heterochromatin integrity and genomic stability under physiological conditions. We further explore the pathogenesis of ATRX-deficient tumors and ATRX syndrome, systematically evaluate current therapeutic strategies for these conditions, and propose novel perspectives on potential targeted therapies for ATRX-mutated malignancies. This review provides useful resource for regarding the etiology and treatment of ATRX deficiency-related diseases.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108537"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tale of two drugs: Molnupiravir and Paxlovid","authors":"Michael D. Waters ,&nbsp;Stafford G. Warren","doi":"10.1016/j.mrrev.2025.108533","DOIUrl":"10.1016/j.mrrev.2025.108533","url":null,"abstract":"<div><div>The orally administered antiviral drug Lagevrio or molnupiravir (MOV) and the combination antiviral drug nirmatrelvir/ritonavir or Paxlovid (PAX) have been shown to reduce the likelihood of hospitalization and death for high-risk patients with COVID-19. Clinical studies, including those comparing PAX and MOV, were reviewed; both drugs are effective in reducing morbidity and mortality in COVID patients, although PAX generally appears to be more efficacious. Both drugs received Emergency Use Authorization in the United States for mild to moderate COVID-19 infection, while only PAX has subsequently been given full FDA approval. The principal disadvantage of PAX is that it interacts with many commonly used drugs, while MOV does not. The purpose of this review is to summarize current information and knowledge about these two drugs. The two drugs have completely different mechanisms of action. PAX inhibits viral replication while MOV induces viral replication errors that are expected to lead to viral inactivation. There is, however, the potential that MOV also could mutate host DNA and cause the virus to mutate into variants with new features. The package insert for MOV states that patients should be notified of relevant toxicity issues before administration. Sensitive mutation detection/analysis studies, such as error corrected Next Generation Sequencing (ecNGS) or HPRT mutation detection assays, in MOV-treated patients are needed to establish the safety of MOV.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108533"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding complexity: The role of long-read sequencing in unraveling genetic disease etiologies","authors":"Ran Xu ,&nbsp;Mengmeng Zhang ,&nbsp;Xiaoming Yang ,&nbsp;Weiming Tian ,&nbsp;Changyan Li","doi":"10.1016/j.mrrev.2024.108529","DOIUrl":"10.1016/j.mrrev.2024.108529","url":null,"abstract":"<div><div>In recent years, next-generation high-throughput sequencing technology has been widely used in clinical practice for the identification and diagnosis of Mendelian diseases as an auxiliary detection method. Nevertheless, due to the limitations in read length and poor coverage of complex genomic regions, the etiology of many genetic diseases is unclear. Long-read sequencing (LRS) addresses these limitations of next-generation sequencing. LRS is an effective tool for the clinical study of the etiology of complex genetic diseases. In this review, we summarized the current research on the application of LRS in diseases across various systems. We also reported the improvements in the diagnostic rate and common variant types of LRS in different studies, providing a foundation for the discovery of new disease mechanisms, which is anticipated to play a crucial role in future research on genetic diseases.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108529"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The landscape of FGFR-TACC fusion in adult glioblastoma: From bench to bedside","authors":"Jing Liu,&nbsp;Zheng Wang","doi":"10.1016/j.mrrev.2025.108536","DOIUrl":"10.1016/j.mrrev.2025.108536","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a lethal central nervous system tumor, characterized by extensive genomic alterations and high intra-tumoral heterogeneity. Gene fusions, derived from chromosomal translocations, deletions, and inversions, were increasingly recognized as key carcinogenic events, with the highest frequency of FGFR-TACC fusion in glioblastoma. As reported, FGFR3-TACC3 fusion mostly coexists with wild-type IDH status, and associates with better prognosis. Mechanistically, FGFR3-TACC3 fusions can constitutively activate non-canonical FGFR downstream pathways, induce aneuploidy, and participate in mitochondrial metabolism, thereby promoting cell proliferation and tumorigenesis. These functions, whether based on FGFR3 phosphorylation or not, are predominantly attributed to the specific domain of TACC3 that involved in regulating the localization and activation of fusion products. Several preclinical studies and clinical trials are being performed to evaluate the efficacy and safety of the FGFR-TACC fusion as a personalised therapeutic target, including the treatments with tyrosine kinase inhibitors, metabolic inhibitors, HSP90 inhibitors, coiled-coil peptide-mimetics, and targeted protein degraders. A subset of populations with FGFR-TACC-positive glioblastoma, after refined molecular screening strategies, may benefit from targeted therapies. Despite major progress in biotechnology, our understanding on the role of fusion events in glioblastoma represented by the FGFR-TACC is still in its infancy. Here, we highlight recent progress on FGFR-TACC fusion in human glioblastoma, emphasizing their molecular mechanisms and potential clinical value.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108536"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inverse dose protraction effects of high-LET radiation: Evidence and significance","authors":"Nobuyuki Hamada ,&nbsp;Yusuke Matsuya ,&nbsp;Lydia B. Zablotska ,&nbsp;Mark P. Little","doi":"10.1016/j.mrrev.2025.108530","DOIUrl":"10.1016/j.mrrev.2025.108530","url":null,"abstract":"<div><div>Biological effects of ionizing radiation vary with radiation quality, which is often expressed as the amount of energy deposited per unit length, i.e., linear energy transfer (LET). For acute irradiation, high-LET radiation generally produces greater biological effects than low-LET radiation, but little knowledge exists as to how dose protraction modifies effects. In this regard, inverse dose protraction effects (IDPEs) are phenomena in which dose protraction enhances effects, contrasting with sparing dose protraction effects in which dose protraction reduces effects. Here, we review the current knowledge on IDPEs of high-LET radiation. To the best of our knowledge, since 1967, 80 biology or epidemiology papers have reported IDPEs following external or internal high-LET irradiation with neutrons, deuterons, α-particles, light ions, or heavy ions. IDPEs of high-LET radiation have been described for biochemical changes in cell-free macromolecules, neoplastic transformation, cell death, DNA damage responses and gene expression changes in mammalian cell cultures of human or rodent origin, gene mutations, cytogenetic changes, cancer, non-cancer effects (e.g., testicular effects, cataracts, cardiovascular diseases) and life shortening in non-human mammals (rodents and dogs), and induction of lung cancer and bone tumors in humans. For external irradiation of mammalian cells in vitro and mammals in vivo, IDPEs of low- and high-LET radiation have been reported for radiation doses spanning in excess of three or four orders of magnitude in slightly different ranges, and for radiation dose rates both spanning over six orders of magnitude in different ranges. IDPEs of high-LET radiation in humans have been reported following internal exposure, but not external exposure. Manifestations and mechanisms of IDPEs of high-LET radiation are far less understood than those of low-LET radiation, warranting further studies that will be pivotal to assess the implications for radiation protection.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108530"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HCN4 and arrhythmias: Insights into base mutations","authors":"Wei Fan ,&nbsp;Xuemei Sun ,&nbsp;Ruoran Yuan ,&nbsp;Xiaojie Hou ,&nbsp;Juyi Wan ,&nbsp;Bin Liao","doi":"10.1016/j.mrrev.2025.108534","DOIUrl":"10.1016/j.mrrev.2025.108534","url":null,"abstract":"<div><div>In the human sinoatrial node (SAN), HCN4 is the primary subtype among the four HCN (hyperpolarization activated cyclic nucleotide-gated) family subtypes. A tetramer of HCN subunits forms the ion channel conducting the hyperpolarization-activated “funny” current (I_f), which plays an important regulatory role in maintaining the pacemaker activity of the SAN. With the advancement of detection technologies over the past 20 years, the relationship between base mutations in the <em>HCN4</em> gene encoding the HCN4 protein and arrhythmias has been continuously elucidated. The expression and kinetic changes of mutated channels were investigated in COS-7, CHO, HEK-293T cells, and Xenopus oocytes, but their functional changes were not elucidated in human myocardial cells. New genome editing methods, such as Base editor and Prime editor, use components of the CRISPR system and other enzymes to directly install single-gene mutation into cellular DNA without causing double-stranded DNA breaks, which reproduce and correct base mutations. In this review, we summarize all base mutations of the <em>HCN4</em> gene, discuss the clinical characteristics and function of some base mutations, and combine base editors to explore the establishment of disease models and the potential for future gene correction.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108534"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The functional regulation between extracellular vesicles and the DNA damage responses","authors":"Jinyi Han ,&nbsp;Kexin Xu ,&nbsp;Ting Xu ,&nbsp;Qin Song ,&nbsp;Ting Duan ,&nbsp;Jun Yang","doi":"10.1016/j.mrrev.2025.108532","DOIUrl":"10.1016/j.mrrev.2025.108532","url":null,"abstract":"<div><div>The DNA damage response (DDR) is a crucial regulatory mechanism for the survival of organisms, and irregularity of DDR may contribute to the development of various diseases, including tumors, making it is a prominent topic in therapeutic research. Extracellular vesicles (EVs), as important mediators of intercellular communication, have been extensively studied in recent years. Notably, an increasing number of studies have revealed a strong connection between DDR and EVs. On one hand, DNA damage affects the release of EVs and their compositional content; on the other hand, EVs can dictate cell survival or death by modulating DDR in both the parental and the recipient cells. This review outlines current progress in the inter-regulatory relationship between EVs and DDR, with special emphasis on the effects of EVs derived from various sources on DDR in recipient cells. In addition, the potential applications of EVs in research and tumor therapy are discussed.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108532"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inverse dose protraction effects of low-LET radiation: Evidence and significance","authors":"Nobuyuki Hamada ,&nbsp;Yusuke Matsuya ,&nbsp;Lydia B. Zablotska ,&nbsp;Mark P. Little","doi":"10.1016/j.mrrev.2025.108531","DOIUrl":"10.1016/j.mrrev.2025.108531","url":null,"abstract":"<div><div>Biological effects of ionizing radiation vary not merely with total dose but also with temporal dose distribution. Sparing dose protraction effects, in which dose protraction reduces effects of radiation have widely been accepted and generally assumed in radiation protection, particularly for stochastic effects (e.g., solid cancer). In contrast, inverse dose protraction effects (IDPEs) in which dose protraction enhances radiation effects have not been well recognized, nor comprehensively reviewed. Here, we review the current knowledge on IDPEs of low linear energy transfer (LET) radiation. To the best of our knowledge, since 1952, 157 biology, epidemiology or clinical papers have reported IDPEs following external or internal low-LET irradiation with photons (X-rays, γ-rays), β-rays, electrons, protons or helium ions. IDPEs of low-LET radiation have been described for biochemical changes in cell-free macromolecules (DNA, proteins or lipids), DNA damage responses in bacteria and yeasts, DNA damage, cytogenetic changes, neoplastic transformation and cell death in mammalian cell cultures of human, rodent or bovine origin, mutagenesis in silkworms, cytogenetic changes, induction of cancer (solid tumors and leukemia) and non-cancer effects (male sterility, cataracts and diseases of the circulatory system), tumor inactivation and survival in non-human mammals (rodents, rabbits, dogs and pigs), and induction of cancer and non-cancer effects (skin changes and diseases of the circulatory system) in humans. In contrast to a growing body of phenomenological evidence for manifestations of IDPEs, there is limited knowledge on mechanistic underpinnings, but proposed mechanisms involve cell cycle-dependent resensitization and low dose hyper-radiosensitivity. These necessitate continued studies for further mechanistic developments and assessment of implications of scientific evidence for radiation protection (e.g., in terms of a dose rate effectiveness factor).</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108531"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging pollutants in the aquatic environments: A review of genotoxic impacts","authors":"Juliana Picinini-Zambelli ,&nbsp;Ana Letícia Hilário Garcia ,&nbsp;Juliana Da Silva","doi":"10.1016/j.mrrev.2024.108519","DOIUrl":"10.1016/j.mrrev.2024.108519","url":null,"abstract":"<div><div>Urbanization and industrial growth have negatively impacted water quality, raising concerns about emerging aquatic pollutants. Despite advancements in water treatment, these substances persist, endangering aquatic life and human health. Although research has focused on the physiological effects of these pollutants, their genetic damage potential remains poorly understood. This systematic review aimed to consolidate existing knowledge on the genotoxic potential of emerging aquatic pollutants. A comprehensive search was conducted across major databases, encompassing articles published from 2001 to 2022. The review primarily focused on research articles that evaluated genotoxicity in environmental samples containing emerging pollutants, as well as in vitro studies using various concentrations of these substances. Fourteen articles were included in the review, with pharmaceutical compounds, personal care products, disinfection byproducts, and industrial chemicals being the most extensively investigated classes. Other notable pollutants included metals, cyanotoxins, antiseptics, pesticides, and caffeine. All these pollutants classes were found to cause DNA damage, either in vitro at specific concentrations or in complex environmental mixtures. The comet assay was the most frequently used method, owing to its sensitivity and practicality in assessing DNA damage. For some pollutants, different responses were observed when comparing in vitro and in vivo studies, emphasizing the need for studies employing both approaches. However, the limited number of available articles underscores the necessity for further research on the genotoxic potential of emerging pollutants. More research is required to clarify mutagenicity, DNA repair kinetics, and cumulative effects of pollutants, which are critical for shaping policies and ensuring safe water quality. A greater knowledge about these pollutants will enable better understanding risk mitigation, ultimately protecting public health and ecosystems.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108519"},"PeriodicalIF":6.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal expansion of cancer driver gene mutants investigated using advanced sequencing technologies","authors":"Barbara L. Parsons","doi":"10.1016/j.mrrev.2024.108514","DOIUrl":"10.1016/j.mrrev.2024.108514","url":null,"abstract":"<div><div>Advanced sequencing technologies (ASTs) have revolutionized the quantitation of cancer driver mutations (CDMs) as rare events, which has utility in clinical oncology, cancer research, and cancer risk assessment. This review focuses on studies that have used ASTs to characterize clonal expansion (CE) of cells carrying CDMs and to explicate the selective pressures that shape CE. Importantly, high-sensitivity ASTs have made possible the characterization of mutant clones and CE in histologically normal tissue samples, providing the means to investigate nascent tumor development. Some ASTs can identify mutant clones in a spatially defined context; others enable integration of mutant data with analyses of gene expression, thereby elaborating immune, inflammatory, metabolic, and/or stromal microenvironmental impacts on CE. As a whole, these studies make it clear that a startlingly large fraction of cells in histologically normal tissues carry CDMs, CDMs may confer a context-specific selective advantage leading to CE, and only a small fraction of cells carrying CDMs eventually result in neoplasia. These observations were integrated with available literature regarding the mechanisms underlying clonal selection to interpret how measurements of CDMs and CE can be interpreted as biomarkers of cancer risk. Given the stochastic nature of carcinogenesis, the potential functional latency of driver mutations, the complexity of potential mutational and microenvironmental interactions, and involvement of other types of genetic and epigenetic changes, it is concluded that CDM-based measurements should be viewed as probabilistic rather than deterministic biomarkers. Increasing inter-sample variability in CDM levels (as a consequence of CE) may be interpretable as a shift away from normal tissue homeostasis and an indication of increased future cancer risk, a process that may reflect normal aging or carcinogen exposure. Consequently, analyses of variability in levels of CDMs have the potential to bolster existing approaches for carcinogenicity testing.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"794 ","pages":"Article 108514"},"PeriodicalIF":6.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}