Mutation Research-Reviews in Mutation Research最新文献

{"title":"Spectrum of BRCA1/2 pathogenic variants in Southern and Western Asia-a systematic review","authors":"Samra Khan ,&nbsp;Ikram A. Burney ,&nbsp;Mahrukh Nasir ,&nbsp;Humaira Saleem ,&nbsp;Muhammad Irfan ,&nbsp;Muhammad Shakeel ,&nbsp;Ishtiaq Ahmad Khan","doi":"10.1016/j.mrrev.2025.108549","DOIUrl":"10.1016/j.mrrev.2025.108549","url":null,"abstract":"<div><div><em>BRCA1</em>/2 germline variants account for 5–10 % of breast cancers (BC) or up to 25 % of hereditary breast cancers, yet data on their prevalence in South Asia and the Middle East remains limited. This study investigates germline <em>BRCA1/2</em> pathogenic variants (PVs) in eight South Asian Association for Regional Cooperation (SAARC) and six Gulf Cooperation Council (GCC) countries, providing insights into the regional mutation landscape. Systematic literature search identified 46 studies and all reported <em>BRCA1</em>/2 variants from each study were re-interpreted using ClinVar and <em>BRCA</em> Exchange to determine pathogenicity. In both cohorts, the median age of BC diagnosis was &lt; 40 years. A total of 159 <em>BRCA1</em> and 100 <em>BRCA2</em> PVs were reported in 772 index South Asian and Middle Eastern BC cases. Only 10 <em>BRCA1/2</em> PVs (6 %) overlapped between the two cohorts, while 141 <em>BRCA1</em> and 98 <em>BRCA2</em> PVs were exclusive to either SAARC or GCC cohorts. <em>BRCA1</em> c.68_69del was the most recurrent PV (n = 111). Overall, <em>BRCA1</em> PVs were prevalent in early-onset (83 %), triple-negative (95 %), and familial BC disease (80 %). In SAARC cohort, <em>BRCA1</em> exon 11 and <em>BRCA2</em> exon 15 were most frequently mutated exons. In GCC cohort, exon 18 of <em>BRCA1</em> and <em>BRCA2</em> exon 13 were the hotspot regions. Our findings highlight the necessity for population-specific genetic testing and indicate a clear regional genetic propensity in <em>BRCA</em> gene. To our knowledge, this dataset represents the largest collection of <em>BRCA1/2</em> PVs from SAARC and GCC nations, and may act as a resource for future studies.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108549"},"PeriodicalIF":6.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340573","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":"Nutritional bioactive compounds with beneficial effects for multiple sclerosis: Potential implication of G-Quadruplexes?","authors":"Anna Maria Malfitano,&nbsp;Giuliano Castellano,&nbsp;Alessandra Croce,&nbsp;Fabiana Napolitano,&nbsp;Giuseppe Portella,&nbsp;Francesco Beguinot,&nbsp;Pietro Formisano,&nbsp;Francesca Fiory","doi":"10.1016/j.mrrev.2025.108548","DOIUrl":"10.1016/j.mrrev.2025.108548","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an autoimmune neurodegenerative disease resulting in myelin destruction and consequent physical disability. Several nutritional molecules modulate genes of reported relevance in MS eliciting beneficial effects. Intriguingly, some of these molecules are able to bind G-Quadruplexes (G4), specific DNA secondary structures involved in the regulation of gene expression and function. For instance, epigallocatechingallate and thymoquinone are known to interact with G4 <em>in vitro</em>, while sanguinarine, quercetin, curcumin and coumarin-quinolinium derivatives interact with G4 <em>in vivo</em> affecting oncogene expression. Noteworthy, several genes involved in MS present G-rich sequences known to fold into G4. Thus, we suggest and speculate that G4 targeting through daily intake of nutritional bioactive molecules might represent a novel therapeutic approach to improve MS symptoms and progression.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108548"},"PeriodicalIF":6.4,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250561","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":"Exposure to radiofrequency electromagnetic fields and IARC carcinogen assessment: Risk of Bias preliminary literature assessment for 10 key characteristics of human carcinogens","authors":"Myrtill Simkó ,&nbsp;Michael H. Repacholi ,&nbsp;Kenneth R. Foster ,&nbsp;Mats-Olof Mattsson ,&nbsp;Rodney J. Croft ,&nbsp;Maria Rosaria Scarfi ,&nbsp;Vijayalaxmi","doi":"10.1016/j.mrrev.2025.108545","DOIUrl":"10.1016/j.mrrev.2025.108545","url":null,"abstract":"<div><div>This is the first assessment of evidence needed to determine whether exposure to radiofrequency electromagnetic fields (RF-EMF) exposures, below the levels recommended in the ICNIRP (2020) guidelines, can influence any of the ten key characteristics (KCs) of human carcinogens developed by the International Agency for Research on Cancer (IARC). We define the 10 KCs and their relevance to carcinogenesis; review in vivo and in vitro studies relevant to the KCs; and conduct a risk of bias (RoB) analysis using 6 criteria. We did not include KC studies on genotoxicity or oxidative stress since Romeo et al. (2024) and Meyer et al. (2024) recently published relevant systematic reviews, but note their respective conclusions. From the other 8 KCs we identified 119 in vitro and 40 in vitro measurements of in vivo studies through 30 June 2023, with 38 % reporting statistically significant effects of exposure. We identified a strong association between the quality of study and outcome, with those meeting more RoB criteria less likely to report statistically significant effects. Effects were reported over the entire frequency range, exposure levels, and biological endpoints with no apparent pattern of exposure parameters resulting in effects. Only KC10 (alters cell proliferation, cell death or nutrient supply) has sufficient studies to analyse, but the other KCs had few studies and diverse endpoints. A few relatively high-quality positive studies require follow-up through additional targeted studies. The heterogeneity and overall poor study quality suggest the need for high-quality studies on these endpoints, preferably adhering to standards such as the Organization for Economic Co-operation and Development [28].</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108545"},"PeriodicalIF":6.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147331","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":"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":"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":"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":"Eco-genotoxicology: A personal reflection","authors":"Awadhesh N. Jha","doi":"10.1016/j.mrrev.2025.108535","DOIUrl":"10.1016/j.mrrev.2025.108535","url":null,"abstract":"<div><div>This reflective commentary provides a personal viewpoint of developments, over the last 3 decades, in the relatively new, multidisciplinary field of ‘eco-genotoxicology,’ also called ‘genetic ecotoxicology’. It aims to outline the scope of the subject area in relation to the historical development of the discipline, critically categorising accomplishments made, taking into account the available information. It also recognises limitations of the existing information and difficulties encountered in this challenging field. Where appropriate, the article makes comparisons to the advances made in human genetic toxicology and radiation biology. The article critically covers the applications of prevailing and emerging tools being used in the field, such as omics, in vitro methodologies, modelling approaches, and artificial intelligence (AI). It also identifies potential areas of development and attempts to credit some of the important personal contributions made in this exciting and challenging subject in relation to human and environmental health.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108535"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054728","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}