Mutation Research-Reviews in Mutation Research最新文献

{"title":"Launching the “Projections” series in mutation research reviews with a special issue on next generation sequencing","authors":"Catherine B. Klein, 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}

{"title":"Inflammatory cytokine storms severity may be fueled by interactions of micronuclei and RNA viruses such as COVID-19 virus SARS-CoV-2. A hypothesis","authors":"Micheline Kirsch-Volders ,&nbsp;Michael Fenech","doi":"10.1016/j.mrrev.2021.108395","DOIUrl":"10.1016/j.mrrev.2021.108395","url":null,"abstract":"<div><p>In this review we bring together evidence that (i) RNA viruses are a cause of chromosomal instability and micronuclei (MN), (ii) those individuals with high levels of lymphocyte MN have a weakened immune response and are more susceptible to RNA virus infection and (iii) both RNA virus infection and MN formation can induce inflammatory cytokine production. Based on these observations we propose a hypothesis that those who harbor elevated frequencies of MN within their cells are more prone to RNA virus infection and are more likely, through combined effects of leakage of self-DNA from MN and RNA from viruses, to escalate pro-inflammatory cytokine production via the cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING) and the Senescence Associated Secretory Phenotype (SASP) mechanisms to an extent that is unresolvable and therefore confers high risk of causing tissue damage by an excessive and overtly toxic immune response. The corollaries from this hypothesis are (i) those with abnormally high MN frequency are more prone to infection by RNA viruses; (ii) the extent of cytokine production and pro-inflammatory response to infection by RNA viruses is enhanced and possibly exceeds threshold levels that may be unresolvable in those with elevated MN levels in affected organs; (iii) reduction of MN frequency by improving nutrition and life-style factors increases resistance to RNA virus infection and moderates inflammatory cytokine production to a level that is immunologically efficacious and survivable.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108395"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10490855","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":"Loss of Y chromosome: An emerging next-generation biomarker for disease prediction and early detection?","authors":"Xihan Guo ,&nbsp;Jianfei Li ,&nbsp;Jinglun Xue ,&nbsp;Michael Fenech ,&nbsp;Xu Wang","doi":"10.1016/j.mrrev.2021.108389","DOIUrl":"10.1016/j.mrrev.2021.108389","url":null,"abstract":"<div><p>As human life expectancy increases substantially and aging is the primary risk factor for most chronic diseases, there is an urgent need for advancing the development of post-genomic era biomarkers that can be used for disease prediction and early detection (DPED). Mosaic loss of Y chromosome (LOY) is the state of nullisomy Y in sub-groups of somatic cells acquired from different post-zygotic development stages and onwards throughout the lifespan. Multiple large-cohort based epidemiology studies have found that LOY in blood cells is a significant risk factor for future mortality and various diseases in males. Many features intrinsic to LOY analysis may be leveraged to enhance its use as a non-invasive, sensitive, reliable, high throughput-biomarker for DPED. Here, we review the emerging literatures in LOY studies and highlight ten strengths for using LOY as a novel biomarker for genomics-driven DPED diagnostics. Meanwhile, the current limitations in this area are also discussed. We conclude by identifying some important knowledge gaps regarding the consequences of malsegregation of the Y chromosome and propose further steps that are required before clinical implementation of LOY. Taken together, we think that LOY has substantial potential as a biomarker for DPED, despite some hurdles that still need to be addressed before its integration into healthcare becomes acceptable.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"788 ","pages":"Article 108389"},"PeriodicalIF":5.3,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mrrev.2021.108389","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715534","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}