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":"2025-07-01","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":"2025-07-01","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":"KRAS oncogenic mutations in benign tumors: adenomatoid odontogenic tumor as a model","authors":"Bruna Pizziolo Coura ,&nbsp;Letícia Martins Guimarães ,&nbsp;Ricardo Santiago Gomez ,&nbsp;Carolina Cavaliéri Gomes","doi":"10.1016/j.mrrev.2025.108552","DOIUrl":"10.1016/j.mrrev.2025.108552","url":null,"abstract":"<div><div>The KRAS protein is a GTPase that plays a role in the MAPK/ERK signaling pathway and <em>KRAS</em> is one of the most frequently mutated proto-oncogenes in malignant neoplasms, including aggressive tumors such as lung, pancreatic, and colorectal cancer. Mutations in <em>KRAS</em>, previously considered oncogenic drivers and hallmarks of cancer, have been observed at a high frequency in benign sporadic tumors, including those with negligible potential for malignant transformation. In line with that, <em>KRAS</em> mutations have recently been shown to be highly prevalent in adenomatoid odontogenic tumor (AOT). In the present paper, we review the spectrum of <em>KRAS</em> mutations reported in AOT to date and discuss the context dependence of KRAS oncogenicity. <em>KRAS</em> p.G12V and p.G12R mutations have been reported in approximately 70 % of AOT cases. The fact that the same spectrum of <em>KRAS</em> mutations is found in tumors with diverse clinical behavior reinforces the tissue and context specificity of <em>KRAS</em> mutation effects. Genome-wide-based future studies may provide clarification on the molecular pathogenesis of the <em>KRAS</em> wild-type cases, and could potentially unravel additional genetic events in mutation-positive cases. In this scenario, the clarification of the molecular pathogenesis of AOT, a benign tumor of indolent behavior, sheds light into how <em>KRAS</em> oncogenic mutations exert distinct effects depending on the biological context.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108552"},"PeriodicalIF":6.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144569916","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":"Trichothiodystrophy: Molecular insights and mechanisms of pathogenicity","authors":"Manuela Lanzafame,&nbsp;Francesca Brevi,&nbsp;Gaia Veniali,&nbsp;Elena Botta","doi":"10.1016/j.mrrev.2025.108555","DOIUrl":"10.1016/j.mrrev.2025.108555","url":null,"abstract":"<div><div>Trichothiodystrophy (TTD) is a rare hereditary disease characterized by brittle, sulphur deficient hair associated with a wide and varied spectrum of clinical features which include skin alterations, neurodevelopmental defects, and immune dysfunction. The presence of hypersensitivity to UV light defines the two main forms of TTD: photosensitive (PS-TTD) and non-photosensitive (NPS-TTD). The disease arises from mutations in a variety of genes involved in different biological processes. Affected processes include DNA repair, transcription as well as translation. This review provides the latest vision of TTD: from up-to-date mutational spectra and genotype-phenotype relationships to our current understanding of the pathogenic mechanisms that underlie the complex etiology of this multi-faceted disease.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108555"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144722411","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":"Acute and chronic inflammation in firefighters: A narrative review","authors":"Giselle L. Allsopp ,&nbsp;Luana C. Main","doi":"10.1016/j.mrrev.2025.108569","DOIUrl":"10.1016/j.mrrev.2025.108569","url":null,"abstract":"<div><div>In 2022, an International Agency for Research on Cancer (IARC) Monographs Working Group assessed the carcinogenic hazard of occupational exposure as a firefighter. The working group concluded that occupational exposure as a firefighter is carcinogenic to humans and identified chronic inflammation as a contributing factor. This review therefore aimed to summarise the evidence of acute and chronic inflammation in firefighters. Acute and chronic (&gt;2–6 weeks) levels inflammatory markers (Eg. Interleukin (IL) 1β, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNFα), C reactive protein (CRP)) were examined in firefighters following exposure to typical firefighting duties including structural and wildland fires. Experimental studies without exposure to combustion emissions were also reviewed to examine the specific contribution of heat exposure, physical exertion, cognitive load and restricted sleep to inflammation in firefighters. For chronic inflammation, the strongest evidence existed for elevated circulating IL-6 (n = 5 studies), followed by elevated IL-1β (n = 3), CRP (n = 3) and IL-8 (n = 2). Acute elevations in IL-6 (n = 8 studies), IL-8 (n = 7) and IL-1β (n=4) were also evident in firefighters in the hours and days following exposure to structural and wildland fires. Experimental studies provided evidence that physical exercise and heat contribute to acute elevations in IL-6 (n = 6) and TNFα (n = 3). In summary, the data reviewed provide strong support that typical firefighting duties can induce both acute and chronic inflammation. More work is needed to determine the prevalence of inflammation in firefighters and to identify mitigating strategies to lower the risk of firefighters developing inflammatory related-chronic disease.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108569"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566224","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":"LRP1B in cancer: From a mutation landscape to predictive biomarkers for precision oncology","authors":"Likun Yang ,&nbsp;Ximo Wang ,&nbsp;Xiangyang Yu ,&nbsp;Jing Xun","doi":"10.1016/j.mrrev.2025.108568","DOIUrl":"10.1016/j.mrrev.2025.108568","url":null,"abstract":"<div><div>Low-density lipoprotein receptor-related protein 1B (LRP1B) is one of the most frequently mutated genes across a wide range of malignancies and has garnered increasing attention owing to its crucial role in tumorigenesis and clinical outcomes. Emerging evidence suggests that LRP1B mutations not only disrupt essential cellular processes such as proliferation, migration, and genomic stability but also significantly impact antigen presentation, modulation of the tumor immune microenvironment, and responses to immunotherapy. These findings highlight its substantial biological and clinical significance. Notably, the mutational landscape of LRP1B exhibits marked tissue specificity and molecular subtype heterogeneity, which may influence the efficacy of immunotherapy, targeted therapies, and cytotoxic chemotherapy. In this review, we provide a comprehensive overview of the mutation patterns, mechanistic functions, immunological roles, and therapeutic predictive value of LRP1B across various cancer types, with the aim of supporting its development as a biomarker and therapeutic target in precision oncology.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"796 ","pages":"Article 108568"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145497089","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":"All roads lead to mitosis: A common requirement for DNA replication stress-dependent and -independent killing of BRCA-deficient cells.","authors":"Sebastian Omar Siri, Ariel Abramovici Blasco, Ginette Moyano, María Candelaria Mares Ahlers, Vanesa Gottifredi","doi":"10.1016/j.mrrev.2025.108557","DOIUrl":"10.1016/j.mrrev.2025.108557","url":null,"abstract":"<p><p>The deficiency in breast cancer associated proteins 1 and 2 (BRCA1 and 2) causes an early and more frequent onset of tumor genesis and progression. Poly (ADP-ribose) polymerase inhibitors (PARPi) are selectively toxic towards BRCA1 and 2-deficient tumors, sparing the healthy cells from patients from side effects. In BRCA1 and 2 deficient tumors, PARPi-mediated cell death is characterized by the augmentation of replication stress (RS) and chromosome instability (CIN) including micronuclei (MN) accumulation, a source of swift genomic rearrangements. PARPi also cause resistance to treatments which indicates the need of treatment alternatives. In this review, we discuss potential options that, similarly to PARPi, selectively kill BRCA1 and/or 2 deficient tumors. Remarkably, while many of those alternatives also upregulate MN and other CIN variables, others cause a RS-independent and MN-independent cell killing. This is the case of the inhibitors of Rho-kinase (ROCK) and, potentially, mitotic kinase Polo like kinase 1 (PLK1). Such a mode of cell killing could be advantageous if attempting to either prevent or postpone the rise of resistance clones in the tumor population that survives the treatment.</p>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":" ","pages":"108557"},"PeriodicalIF":4.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765736","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":"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":"2025-01-01","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":"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}