Mutation Research-Reviews in Mutation Research最新文献

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Spectrum of BRCA1/2 pathogenic variants in Southern and Western Asia-a systematic review 南亚和西亚BRCA1/2致病变异谱——系统综述

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-06-20 DOI: 10.1016/j.mrrev.2025.108549

Samra Khan , Ikram A. Burney , Mahrukh Nasir , Humaira Saleem , Muhammad Irfan , Muhammad Shakeel , Ishtiaq Ahmad Khan

BRCA1/2 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 BRCA1/2 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 BRCA1/2 variants from each study were re-interpreted using ClinVar and BRCA Exchange to determine pathogenicity. In both cohorts, the median age of BC diagnosis was < 40 years. A total of 159 BRCA1 and 100 BRCA2 PVs were reported in 772 index South Asian and Middle Eastern BC cases. Only 10 BRCA1/2 PVs (6 %) overlapped between the two cohorts, while 141 BRCA1 and 98 BRCA2 PVs were exclusive to either SAARC or GCC cohorts. BRCA1 c.68_69del was the most recurrent PV (n = 111). Overall, BRCA1 PVs were prevalent in early-onset (83 %), triple-negative (95 %), and familial BC disease (80 %). In SAARC cohort, BRCA1 exon 11 and BRCA2 exon 15 were most frequently mutated exons. In GCC cohort, exon 18 of BRCA1 and BRCA2 exon 13 were the hotspot regions. Our findings highlight the necessity for population-specific genetic testing and indicate a clear regional genetic propensity in BRCA gene. To our knowledge, this dataset represents the largest collection of BRCA1/2 PVs from SAARC and GCC nations, and may act as a resource for future studies.

BRCA1/2种系变异占乳腺癌（BC）的5-10%或高达25%的遗传性乳腺癌，但其在南亚和中东的患病率数据仍然有限。本研究调查了8个南亚区域合作联盟（SAARC）和6个海湾合作委员会（GCC）国家的种系BRCA1/2致病变异（pv），为区域突变格局提供了见解。系统文献检索确定了46项研究，并使用ClinVar和BRCA Exchange对每项研究中所有报告的BRCA1/2变异进行重新解释，以确定致病性。在这两个队列中，BC诊断的中位年龄为

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引用次数: 0

Nutritional bioactive compounds with beneficial effects for multiple sclerosis: Potential implication of G-Quadruplexes? 对多发性硬化症有益的营养生物活性化合物：g -四联体的潜在含义？

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-06-06 DOI: 10.1016/j.mrrev.2025.108548

Anna Maria Malfitano, Giuliano Castellano, Alessandra Croce, Fabiana Napolitano, Giuseppe Portella, Francesco Beguinot, Pietro Formisano, Francesca Fiory

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 in vitro, while sanguinarine, quercetin, curcumin and coumarin-quinolinium derivatives interact with G4 in vivo 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.

多发性硬化症（MS）是一种自身免疫性神经退行性疾病，导致髓磷脂破坏和随之而来的身体残疾。一些营养分子调节基因报道相关的MS引发有益的影响。有趣的是，其中一些分子能够结合g -四联体（G4），这是参与基因表达和功能调节的特定DNA二级结构。例如，表没食子儿茶hingallate和百里醌已知在体外与G4相互作用，而血根碱、槲皮素、姜黄素和香豆素-喹啉衍生物在体内与G4相互作用，影响癌基因的表达。值得注意的是，一些与MS相关的基因存在富含g的序列，已知可折叠成G4。因此，我们建议并推测通过每日摄入营养生物活性分子靶向G4可能是改善MS症状和进展的一种新的治疗方法。

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引用次数: 0

Exposure to radiofrequency electromagnetic fields and IARC carcinogen assessment: Risk of Bias preliminary literature assessment for 10 key characteristics of human carcinogens 暴露于射频电磁场与IARC致癌物评估：偏倚风险对人类致癌物的10个关键特征的初步文献评估

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-05-27 DOI: 10.1016/j.mrrev.2025.108545

Myrtill Simkó , Michael H. Repacholi , Kenneth R. Foster , Mats-Olof Mattsson , Rodney J. Croft , Maria Rosaria Scarfi , Vijayalaxmi

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].

这是为确定低于ICNIRP（2020）指南建议水平的射频电磁场（RF-EMF）暴露是否会影响国际癌症研究机构（IARC）制定的人类致癌物十大关键特征（KCs）中的任何一种所需证据的首次评估。我们定义了10种KCs及其与癌变的相关性；回顾与KCs相关的体内和体外研究；并使用6个标准进行偏倚风险（RoB）分析。由于Romeo et al.（2024）和Meyer et al.（2024）最近发表了相关的系统综述，我们没有纳入关于遗传毒性或氧化应激的KC研究，但请注意他们各自的结论。从其他8个KCs中，我们确定了截至2023年6月30日的119个体外和40个体内研究的体外测量，其中38% %报告了统计显着的暴露效应。我们发现研究质量和结果之间存在很强的相关性，那些符合更多RoB标准的研究不太可能报告统计上显著的效果。效应在整个频率范围、暴露水平和生物终点均有报道，没有明显的暴露参数模式导致效应。只有KC10（改变细胞增殖、细胞死亡或营养供应）有足够的研究来分析，但其他KCs的研究很少，终点也不同。一些相对高质量的阳性研究需要通过额外的针对性研究进行随访。异质性和总体较差的研究质量表明，需要对这些终点进行高质量的研究，最好遵循经济合作与发展组织（oecd）等标准。

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From pathology to therapy: A comprehensive review of ATRX mutation related molecular functions and disorders 从病理到治疗：ATRX突变相关分子功能和疾病的综合综述

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01 DOI: 10.1016/j.mrrev.2025.108537

Fan Xu , Daohan Yu , Jiazheng Guo , Jingze Hu , Yunlei Zhao , Chuanlu Jiang , Xiangqi Meng , Jinquan Cai , Yan Zhao

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.

ATRX （α -地中海贫血/智力低下，x连锁）是一种染色质重塑基因，是人类癌症中最常见的突变基因之一。ATRX蛋白作为组蛋白伴侣蛋白，促进组蛋白正确折叠和组装成核小体核心。对其分子机制的研究大大提高了我们对其在染色体不稳定性和DNA修复缺陷相关疾病中的作用的理解。在这篇全面的综述中，我们描述了ATRX在生理条件下维持异染色质完整性和基因组稳定性的关键功能。我们进一步探讨了ATRX缺陷肿瘤和ATRX综合征的发病机制，系统评估了目前针对这些疾病的治疗策略，并提出了针对ATRX突变恶性肿瘤的潜在靶向治疗的新观点。本文综述为ATRX缺乏相关疾病的病因和治疗提供了有益的资源。

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IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01

引用次数: 0

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01

引用次数: 0

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01

引用次数: 0

IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01

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A tale of two drugs: Molnupiravir and Paxlovid 这是一个关于两种药物的故事：莫努匹拉韦和Paxlovid

IF 6.4 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01 DOI: 10.1016/j.mrrev.2025.108533

Michael D. Waters , Stafford G. Warren

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.

口服抗病毒药物Lagevrio或molnupiravir （MOV）和联合抗病毒药物nirmatrelvir/ritonavir或Paxlovid （PAX）已被证明可以降低高危COVID-19患者住院和死亡的可能性。回顾了临床研究，包括比较PAX和MOV的研究；这两种药物都能有效降低COVID - 19患者的发病率和死亡率，尽管PAX通常似乎更有效。这两种药物都在美国获得了用于轻度至中度COVID-19感染的紧急使用授权，而只有PAX随后获得了FDA的全面批准。PAX的主要缺点是它与许多常用药物相互作用，而MOV则没有。本综述的目的是总结目前关于这两种药物的信息和知识。这两种药物的作用机制完全不同。PAX抑制病毒复制，而MOV诱导病毒复制错误，从而导致病毒失活。然而，MOV也有可能使宿主DNA发生突变，导致病毒变异成具有新特征的变体。MOV的包装说明书指出，在给药前应告知患者相关的毒性问题。需要在MOV治疗的患者中进行敏感的突变检测/分析研究，例如纠正错误的下一代测序（ecNGS）或HPRT突变检测试验，以确定MOV的安全性。

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IF 4.2 2区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Reviews in Mutation Research

Pub Date : 2025-01-01

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Mutation Research-Reviews in Mutation Research

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