Mutation Research-Reviews in Mutation Research最新文献

{"title":"Genetic predisposition to lymphomas: Overview of rare syndromes and inherited familial variants","authors":"Bartosz Szmyd,&nbsp;Wojciech Mlynarski,&nbsp;Agata Pastorczak","doi":"10.1016/j.mrrev.2021.108386","DOIUrl":"10.1016/j.mrrev.2021.108386","url":null,"abstract":"<div><p>Approximately 10 % of malignancies occur in carriers of germline<span><span> mutations predisposing to cancer. A high risk of developing lymphomas has been noted in many primary immunodeficiencies, including DNA repair disorders. Moreover, implementation of next-generation sequencing has recently enabled to uncover rare genetic variants predisposing patients to lymphoid neoplasms. Some patients harboring inherited predisposition to lymphomas require dedicated clinical management, which will contribute to effective cancer treatment and to the prevention of potential severe toxicities and secondary malignancies. In line with that, our review summarizes the natural history of </span>lymphoid tumors developing on different germline genetic backgrounds and discusses the progress that has been made toward successfully treating these malignancies.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108386"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714544","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":"Roadmap for translating results from the micronucleus assay into clinical practice: From observational studies to randomized controlled trials","authors":"Stefano Bonassi ,&nbsp;Michael Fenech","doi":"10.1016/j.mrrev.2021.108390","DOIUrl":"10.1016/j.mrrev.2021.108390","url":null,"abstract":"<div><p><span>According to the definition delivred by the WHO, a biomarker, independently from its role that may be indicative of exposure, response or effect, is inevitably linked to a clinical outcome or to a disease. The presence of a continuum from early biological events to therapy, and prognosis is the unifying mechanism that justifies this conclusion. Traditionally, the technical and inter-individual variability of the assays, together with the long duration between early pathogenetic events and the disease, prevented clinical applications to these biomarkers. These limitations became less important with the emerging of personalized preventive medicine because of the focus on disease prediction and prevention, and the recommended use of all data concerning measurable patient's features. Several papers have been published on the best validation procedures for translating biomarkers to real life. The history of cholesterol concentration is extensively discussed as a reliable example of a biomarker that - after a long and controversial validation process - is currently used in clinical practice. The frequency of micronucleated cells is a reliable biomarker for the pathogenesis of cancer and other non-communicable diseases, and the link with clinical outcomes is substantiated by epidemiological evidence and strong mechanistic basis. Available literature concerning the use of the </span>micronucleus assay<span> in clinical studies is discussed, and a suitable three-levels road-map driving this biomarker towards clinical practice is presented. Under the perspective of personalized medicine, the use of the micronucleus assays can play a decisive role in addressing preventive and therapeutic strategies of chronic diseases. In many cases the MN assay is either currently used in clinical practice or classified as adequate to consider translation into practice. The roadmap to clinical validation of the micronucleus assay finds inspiration from the history of biomarkers such as cholesterol, which clearly showed that the evidence from prospective studies or RCTs is critical to achieve the required level of trust from the healthcare profession. (307 words)</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108390"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715535","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":"Launching the “Projections” series in mutation research reviews with a special issue on next generation sequencing","authors":"Catherine B. Klein,&nbsp;Barbara L. Parsons","doi":"10.1016/j.mrrev.2021.108394","DOIUrl":"10.1016/j.mrrev.2021.108394","url":null,"abstract":"","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108394"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715538","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":"Fetomaternal microchimerism and genetic diagnosis: On the origins of fetal cells and cell-free fetal DNA in the pregnant woman","authors":"Margit Rosner ,&nbsp;Thomas Kolbe ,&nbsp;Markus Hengstschläger","doi":"10.1016/j.mrrev.2021.108399","DOIUrl":"10.1016/j.mrrev.2021.108399","url":null,"abstract":"<div><p>During pregnancy several types of fetal cells and fetal stem cells, including pregnancy-associated progenitor cells (PAPCs), traffic into the maternal circulation. Whereas they also migrate to various maternal organs and adopt the phenotype of the target tissues to contribute to regenerative processes, fetal cells also play a role in the pathogenesis of maternal diseases. In addition, cell-free fetal DNA (cffDNA) is detectable in the plasma of pregnant women. Together they constitute the well-known phenomenon of fetomaternal microchimerism, which inspired the concept of non-invasive prenatal testing (NIPT) using maternal blood. An in-depth knowledge concerning the origins of these fetal cells and cffDNA allows a more comprehensive understanding of the biological relevance of fetomaternal microchimerism and has implications for the ongoing expansion of resultant clinical applications.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108399"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1383574221000363/pdfft?md5=f15f8aef6bdddac81db523d6745691af&pid=1-s2.0-S1383574221000363-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39714543","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":"Borderline HbA2 levels: Dilemma in diagnosis of beta-thalassemia carriers","authors":"Stacy Colaco,&nbsp;Anita Nadkarni","doi":"10.1016/j.mrrev.2021.108387","DOIUrl":"https://doi.org/10.1016/j.mrrev.2021.108387","url":null,"abstract":"<div><p>There is inconsistency in the exact definition of diagnostic levels of HbA₂ for β thalassemia trait. While many laboratories consider HbA₂ ≥4.0 % diagnostic, still others consider HbA₂ ≥3.3 % or HbA₂ ≥3.5 % as the cut-off for establishing β thalassemia carrier diagnosis. This is because, over the years, studies have described β thalassemia carriers showing HbA₂ levels that lie above the normal range of HbA₂ but below the typical carrier range of β thalassemia. These, “borderline HbA₂ levels”, though not detrimental to health, are significant in β thalassemia carrier diagnosis because they can lead to misinterpretation of results. In this review, we have evaluated the prevalence of borderline HbA₂ levels and discussed the causes of borderline HbA₂ values. We have also compiled an extensive catalogue of β globin gene defects associated with borderline HbA₂ levels and have discussed strategies to avoid misdiagnosing borderline HbA₂ β thalassemia carriers. Our analysis of studies that have delineated the cause of borderline HbA₂ levels in different populations shows that 35.4 % [626/1766] of all individuals with borderline HbA₂ levels carry a molecular defect. Among the positive samples, 17 % [299/1766] show β globin gene defects, 7.7 % [137/1766] show α thalassemia defects, 2.7 % [49/1766] show KLF1 gene mutations, 2.3 % [41/1766] show the co-inheritance of β and α thalassemia, 2.0 % [37/1766] show the co-inheritance of β and δ thalassemia and 1.8 % [32/1766] show α globin gene triplication. It appears that a comprehensive molecular work up of the β globin gene is the only definite method to detect borderline HbA₂ β thalassemia carriers, especially in populations with a high prevalence of the disease. The presence of associated genetic or acquired determinants may subsequently be assessed to identify the cause of borderline HbA₂.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108387"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72063777","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":"Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms","authors":"Jiaojiao Li ,&nbsp;Chunxiao Sun ,&nbsp;Wenwen Cai ,&nbsp;Jing Li ,&nbsp;Barry P. Rosen ,&nbsp;Jian Chen","doi":"10.1016/j.mrrev.2021.108396","DOIUrl":"10.1016/j.mrrev.2021.108396","url":null,"abstract":"<div><p><span><span>Enzymatic methylation catalyzed by </span>methyltransferases has a significant impact on many human biochemical reactions. As the second most ubiquitous cofactor in humans, S-adenosyl-</span><span>l</span><span><span>-methionine (SAM or AdoMet) serves as a methyl donor for SAM-dependent methyltransferases (MTases), which transfer a methyl group to a </span>nucleophilic<span> acceptor such as O, As, N, S, or C as the byproduct. SAM-dependent methyltransferases can be grouped into different types based on the substrates. Here we systematically reviewed eight types of methyltransferases associated with human diseases. Catechol O-methyltransferase (COMT), As(III) S-adenosylmethionine methyltransferase (AS3MT), indolethylamine </span></span><em>N</em>-methyltransferase (INMT), phenylethanolamine <em>N</em>-methyltransferase (PNMT), histamine <em>N</em><span>-methyltransferase (HNMT), nicotinamide </span><em>N</em><span><span><span><span>-methyltransferase (NNMT), thiopurine S-methyltransferase (TPMT) and DNA methyltansferase (DNMT) are classic SAM-dependent MTases. Correlations between genotypes and disease susceptibility can be partially explained by </span>genetic polymorphisms. The physiological function, </span>substrate specificity, </span>genetic variants and disease susceptibility associated with these eight SAM-dependent methyltransferases are discussed in this review.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108396"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39576790","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":"Evaluation of DNA double-strand break repair capacity in human cells: Critical overview of current functional methods","authors":"Xavier Tatin ,&nbsp;Giovanna Muggiolu ,&nbsp;Sylvie Sauvaigo ,&nbsp;Jean Breton","doi":"10.1016/j.mrrev.2021.108388","DOIUrl":"10.1016/j.mrrev.2021.108388","url":null,"abstract":"<div><p><span><span>DNA double-strand breaks (DSBs) are highly deleterious lesions, responsible for </span>mutagenesis<span>, chromosomal translocation or cell death. DSB repair (DSBR) is therefore a critical part of the DNA damage response (DDR) to restore molecular and genomic integrity. In humans, this process is achieved through different pathways with various outcomes. The balance between DSB repair activities varies depending on cell types, tissues or individuals. Over the years, several methods have been developed to study variations in DSBR capacity. Here, we mainly focus on functional techniques, which provide dynamic information regarding global DSB repair proficiency or the activity of specific pathways. These methods rely on two kinds of approaches. Indirect techniques, such as pulse field gel </span></span>electrophoresis<span><span> (PFGE), the comet assay<span> and immunofluorescence (IF), measure DSB repair capacity by quantifying the time-dependent decrease in DSB levels after exposure to a DNA-damaging agent. On the other hand, cell-free assays and reporter-based methods directly track the repair of an artificial DNA substrate. Each approach has intrinsic advantages and limitations and despite considerable efforts, there is currently no ideal method to quantify DSBR capacity. All techniques provide different information and can be regarded as complementary, but some studies report conflicting results. Parameters such as the type of biological material, the required equipment or the cost of analysis may also limit available options. Improving currently available methods measuring DSBR capacity would be a major step forward and we present direct applications in mechanistic studies, drug development, human </span></span>biomonitoring<span> and personalized medicine, where DSBR analysis may improve the identification of patients eligible for chemo- and radiotherapy.</span></span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108388"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108388","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715533","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":"Genetic polymorphisms on the effectiveness or safety of breast cancer treatment: Clinical relevance and future perspectives","authors":"Yasmin Cura ,&nbsp;Cristina Pérez Ramírez ,&nbsp;Almudena Sánchez Martín ,&nbsp;Fernando Martínez Martínez ,&nbsp;Miguel Ángel Calleja Hernández ,&nbsp;María del Carmen Ramírez Tortosa ,&nbsp;Alberto Jiménez Morales","doi":"10.1016/j.mrrev.2021.108391","DOIUrl":"10.1016/j.mrrev.2021.108391","url":null,"abstract":"<div><p><span><span>Breast cancer (BC) is the most frequent neoplasm and one of the main causes of death in women. The pharmacological treatment of BC consists of hormonal therapy<span>, chemotherapeutic agents and targeted therapy. The response to BC therapy is highly variable in clinical practice. This variability can be explained by the presence of genetic polymorphisms in genes involved in the </span></span>pharmacokinetics<span>, pharmacodynamics or immune response of patients. The abundant evidence of associations between low-activity alleles </span></span><em>CYP2D6*3, *4, *5, *6, *10</em> and <em>*41</em><span> and poor results with tamoxifen therapy, and between </span><span><em>DPYD</em></span><span> gene polymorphisms<span><span> rs3918290, rs55886062, rs67376798 and rs75017182 and increased risk of toxicity to fluoropyrimidine therapy, justify the existence of clinical </span>pharmacogenetic guidelines. The </span></span><em>NQO1</em><span> rs1800566 polymorphism is related to poorer results in BC therapy with chemotherapy agents. The polymorphism rs1695 of the </span><span><em>GSTP1</em></span><span> gene has been associated with the effectiveness and toxicity of fluorouracil<span>, cyclophosphamide<span> and epirubicin therapy. Finally, the </span></span></span><em>HLA-DQA1*02:01</em><span> allele is significantly associated with the occurrence of liver toxicity events in patients receiving lapatinib. There is moderate evidence to support the aforementioned associations and, therefore, a high probability of these being considered as future predictive genetic biomarkers of response. However, further studies are required to reinforce or clarify their clinical relevance.</span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108391"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715536","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":"Genotoxicity of multi-walled carbon nanotube reference materials in mammalian cells and animals","authors":"Peter Møller ,&nbsp;Regitze Sølling Wils ,&nbsp;Emilio Di Ianni ,&nbsp;Claudia Andrea Torero Gutierrez ,&nbsp;Martin Roursgaard ,&nbsp;Nicklas Raun Jacobsen","doi":"10.1016/j.mrrev.2021.108393","DOIUrl":"10.1016/j.mrrev.2021.108393","url":null,"abstract":"<div><p>Carbon nanotubes (CNTs) were the first nanomaterials to be evaluated by the International Agency for Research on Cancer (IARC). The categorization as possibly carcinogenic agent to humans was only applicable to multi-walled carbon nanotubes called MWCNT-7. Other types of CNTs were not classifiable because of missing data and it was not possible to pinpoint unique CNT characteristics that cause cancer. Importantly, the European Commission’s Joint Research Centre (JRC) has established a repository of industrially manufactured nanomaterials that encompasses at least four well-characterized MWCNTs called NM-400 to NM-403 (original JRC code). This review summarizes the genotoxic effects of these JRC materials and MWCNT-7. The review consists of 36 publications with results on cell culture experiments (22 publications), animal models (9 publications) or both (5 publications). As compared to the publications in the IARC monograph on CNTs, the current database represents a significant increase as there is only an overlap of 8 publications. However, the results come mainly from cell cultures and/or measurements of DNA strand breaks by the comet assay and the micronucleus assay (82 out of 97 outcomes). A meta-analysis of cell culture studies on DNA strand breaks showed a genotoxic response by MWCNT-7, less consistent effect by NM-400 and NM-402, and least consistent effect by NM-401 and NM-403. Results from other <em>in vitro</em> tests indicate strongest evidence of genotoxicity for MWCNT-7. There are too few observations from animal models and humans to make general conclusions about genotoxicity.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108393"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108393","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715537","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":"Application of the comet assay for the evaluation of DNA damage in mature sperm","authors":"Goran Gajski ,&nbsp;Sanda Ravlić ,&nbsp;Roger Godschalk ,&nbsp;Andrew Collins ,&nbsp;Maria Dusinska ,&nbsp;Gunnar Brunborg","doi":"10.1016/j.mrrev.2021.108398","DOIUrl":"10.1016/j.mrrev.2021.108398","url":null,"abstract":"<div><p><span><span><span>DNA<span><span> integrity is considered an important parameter of semen quality and is of significant value as a predictor of male fertility. Currently, there are several methods that can assess sperm DNA integrity. One such assay is the </span>comet assay, or single-cell gel electrophoresis, which is a simple, sensitive, reliable, quick and low-cost technique that is used for measuring </span></span>DNA strand<span> breaks and repair at the level of individual cells. Although the comet assay is usually performed with somatic cells<span> from different organs, the assay has the ability to detect genotoxicity in germ cells at different stages of </span></span></span>spermatogenesis. Since the ability of sperm to remove DNA damage differs between the stages, interpretation of the results is dependent on the cells used. In this paper we give an overview on the use and applications of the comet assay on mature sperm and its ability to detect sperm DNA damage in both animals and humans. Overall, it can be concluded that the presence in sperm of significantly damaged DNA, assessed by the comet assay, is related to </span>male infertility and seems to reduce live births. Although there is some evidence that sperm DNA damage also has a long-term impact on offspring’s health, this aspect of DNA damage in sperm is understudied and deserves further attention. In summary, the comet assay can be applied as a useful tool to study effects of genotoxic exposures on sperm DNA integrity in animals and humans.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108398"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39576795","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}