Mutation Research-Reviews in Mutation Research最新文献

{"title":"Clonal evolution and expansion associated with therapy resistance and relapse of colorectal cancer","authors":"Anupriya S ,&nbsp;Averi Chakraborty ,&nbsp;Srinivas Patnaik","doi":"10.1016/j.mrrev.2022.108445","DOIUrl":"10.1016/j.mrrev.2022.108445","url":null,"abstract":"<div><p><span>Colorectal cancer<span><span> (CRC) arises by a continuous process of genetic<span><span> diversification and clonal evolution<span>. Multiple genes and pathways have a role in tumor initiation and progression. The gradual accumulation of genetic and epigenetic processes leads to the establishment of </span></span>adenoma and cancer. The important 'driver' mutations in </span></span>tumor suppressor genes (such as </span></span><span><em>TP53, </em><em>APC</em></span>, and <em>SMAD4</em><span>) and oncogenes (such as </span><span><em>KRAS</em><em>, NRAS, MET</em></span>, and <em>PIK3CA</em><span>) confer selective growth advantages and cause CRC advancement. Clonal evolution induced by therapeutic pressure, as well as intra-tumoral heterogeneity, has been a great challenge in the treatment of metastatic CRC<span>. Tumors often develop resistance to treatments as a result of intra-tumor heterogeneity, clonal evolution, and selection. Hence, the development of a multidrug personalized approach should be prioritized to pave the way for therapeutics repurposing and combination therapy to arrest tumor progression. This review summarizes how selective drug pressure can impact tumor evolution, resulting in the formation of polyclonal resistance mechanisms, ultimately promoting cancer progression. Current strategies for targeting clonal evolution are described. By understanding sources and consequences of tumor heterogeneity, customized and effective treatment plans to combat drug resistance may be devised.</span></span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"790 ","pages":"Article 108445"},"PeriodicalIF":5.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10821104","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":"The contribution of whole-exome sequencing to intellectual disability diagnosis and knowledge of underlying molecular mechanisms: A systematic review and meta-analysis","authors":"Karen Y. Sánchez-Luquez ,&nbsp;Marina Xavier Carpena ,&nbsp;Simone M. Karam ,&nbsp;Luciana Tovo-Rodrigues","doi":"10.1016/j.mrrev.2022.108428","DOIUrl":"10.1016/j.mrrev.2022.108428","url":null,"abstract":"<div><p><span>Whole-exome sequencing (WES) is useful for molecular diagnosis, family genetic counseling<span>, and prognosis of intellectual disability (ID). However, ID molecular diagnosis ascertainment based on WES is highly dependent on </span></span><em>de novo</em><span> mutations (DNMs) and variants of uncertain significance (VUS). The quantification of DNM frequency<span><span> in ID molecular diagnosis ascertainment and the biological mechanisms common to genes with VUS may provide objective information about WES use in ID diagnosis and etiology. We aimed to investigate and estimate the rate of ID molecular diagnostic assessment by WES, quantify the contribution of DNMs to this rate, and biologically and functionally characterize the genes whose mutations were identified through WES. A PubMed/Medline, Web of Science, Scopus, Science Direct, BIREME, and </span>PsycINFO<span> systematic review and meta-analysis was performed, including studies published between 2010 and 2022. Thirty-seven articles with data on ID molecular diagnostic yield using the WES approach were included in the review. WES testing accounted for an overall diagnostic rate of 42% (Confidence interval (CI): 35–50%), while the estimate restricted to DNMs was 11% (CI: 6–18%). Genetic<span> information on mutations and genes was extracted and split into two groups: (1) genes whose mutation was used for positive molecular diagnosis, and (2) genes whose mutation led to uncertain molecular diagnosis. After functional enrichment analysis, in addition to their expected roles in neurodevelopment<span><span>, genes from the first group were enriched in epigenetic regulatory mechanisms, immune system regulation, and circadian rhythm control. Genes from uncertain diagnosis cases were enriched in the renin </span>angiotensin pathway. Taken together, our results support WES as an important approach to the molecular diagnosis of ID. The results also indicated relevant pathways that may underlie the pathogenesis of ID with the renin-angiotensin pathway being suggested to be a potential pathway underlying the pathogenesis of ID.</span></span></span></span></span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"790 ","pages":"Article 108428"},"PeriodicalIF":5.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10452725","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":"Lymphocyte-based challenge DNA-repair assays for personalized health risk assessment","authors":"Tong-shuai Wang ,&nbsp;Mathuros Ruchirawat ,&nbsp;Panida Narasumrit ,&nbsp;Zhao-lin Xia ,&nbsp;William W. Au","doi":"10.1016/j.mrrev.2022.108427","DOIUrl":"10.1016/j.mrrev.2022.108427","url":null,"abstract":"<div><p>Combinations of genetic and environmental factors are responsible for the development of many human diseases, such as cancer, as demonstrated using various biomarkers. Within this scenario, DNA repair holds a gate-keeper position which determines outcomes after appearance of DNA damage and, therefore, adverse cellular consequences, e.g., initiation of carcinogenesis. DNA repair deficiency and some of the subsequent events can be validated from studies using live cells from cancer patients. However, these deficiencies/events are difficult to demonstrate in live cells from normal individuals because individual variations in DNA repair capacities (DRC) are too low to be measured easily. Such lack of information has been hindering progress in developing personalized disease prevention and intervention protocols, especially among exposed populations. However, using a variety of challenge assays as biomarkers, variations in individual’s DRC can be amplified in live cells and be determined. Furthermore, evidence indicates that DRC are not only inherited but can also be modified by environmental factors (e.g., nutritional status and exposure to genotoxic substances). Using these challenge assays, e.g., in live lymphocytes, individual’s DRC can be holistically and functionally determined as well as quantitated. With the more precise information, assessment of health risk can be better determined on an individual rather than on a population basis. This review provides a succinct summary on the development and application of recent challenge assays in lymphocytes which can provide measurements of individuals’ DRC, and on the latest data for more precise disease prevention and intervention.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"790 ","pages":"Article 108427"},"PeriodicalIF":5.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458435","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":"Code inside the codon: The role of synonymous mutations in regulating splicing machinery and its impact on disease","authors":"Avik Sarkar ,&nbsp;Kalpana Panati ,&nbsp;Venkata Ramireddy Narala","doi":"10.1016/j.mrrev.2022.108444","DOIUrl":"10.1016/j.mrrev.2022.108444","url":null,"abstract":"<div><p><span>In eukaryotes, precise pre-mRNA processing, including alternative splicing, is essential to carry out the intricate protein translation<span><span> process. Both point mutations (that alter the translated protein sequence) and synonymous mutations (that do not alter the translated protein sequence) are capable of affecting the splicing process. Synonymous mutations are known to affect gene expression via altering </span>mRNA stability<span>, mRNA secondary structure, splicing processes, and translational kinetics. In higher eukaryotes, precise splicing is regulated by three weakly conserved </span></span></span><em>cis</em>-elements, 5′ and 3′ splice sites and the branch site. Many other <em>cis</em>-acting elements (exonic/intronic splicing enhancers and silencers) and <em>trans</em>-acting splicing factors (serine and arginine-rich proteins and heterogeneous nuclear ribonucleoproteins) have also been found to enhance or suppress the splicing process. The appearance of synonymous mutations in <em>cis</em><span><span>-acting elements can alter the splicing process by changing the binding pattern of splicing factors to exonic splicing enhancers or silencer motifs. This results in </span>exon skipping<span>, intron retention, and various other forms of alternative splicing, eventually leading to the emergence of a wide range of diseases. The focus of this review is to elucidate the role of synonymous mutations and their impact on abnormal splicing mechanisms. Further, this study highlights the function of synonymous mutation in mediating abnormal splicing in cancer and development of X-linked, and autosomal inherited diseases.</span></span></p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"790 ","pages":"Article 108444"},"PeriodicalIF":5.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10821096","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":"Circadian effects on UV-induced damage and mutations","authors":"Donna Goodenow ,&nbsp;Adam J. Greer ,&nbsp;Sean J. Cone ,&nbsp;Shobhan Gaddameedhi","doi":"10.1016/j.mrrev.2022.108413","DOIUrl":"10.1016/j.mrrev.2022.108413","url":null,"abstract":"<div><p><span>Skin cancer is the most diagnosed type of cancer in the United States, and while most of these malignancies are highly treatable, treatment costs still exceed $8 billion annually. Over the last 50 years, the annual incidence of skin cancer has steadily grown; therefore, understanding the environmental factors driving these types of cancer is a prominent research-focus. A causality between ultraviolet radiation<span> (UVR) exposure and skin cancer is well-established, but exposure to UVR alone is not necessarily sufficient to induce carcinogenesis. The emerging field of circadian biology intersects strongly with the physiological systems of the mammalian body and introduces a unique opportunity for analyzing mechanisms of homeostatic disruption. The circadian clock refers to the approximate 24-hour cycle, in which protein levels of specific clock-controlled genes (CCGs) fluctuate based on the time of day. Though these CCGs are tissue specific, the skin has been observed to have a robust circadian clock that plays a role in its response to UVR exposure. This in-depth review will detail the mechanisms of the circadian clock and its role in cellular homeostasis<span>. Next, the skin’s response to UVR exposure and its induction of DNA damage and mutations will be covered – with an additional focus placed on how the circadian clock influences this response through nucleotide excision repair. Lastly, this review will discuss current models for studying UVR-induced </span></span></span>skin lesions and perturbations of the circadian clock, as well as the impact of these factors on human health.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108413"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10739900","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":"XPC multifaceted roles beyond DNA damage repair: p53-dependent and p53-independent functions of XPC in cell fate decisions","authors":"Abir Zebian ,&nbsp;Maya El-Dor ,&nbsp;Abdullah Shaito ,&nbsp;Frédéric Mazurier ,&nbsp;Hamid Reza Rezvani ,&nbsp;Kazem Zibara","doi":"10.1016/j.mrrev.2021.108400","DOIUrl":"10.1016/j.mrrev.2021.108400","url":null,"abstract":"<div><p><span><span>Xeroderma pigmentosum group C protein (XPC) acts as a </span>DNA<span><span><span> damage recognition factor for bulky adducts and as an initiator of global genome nucleotide excision repair (GG-NER). Novel insights have shown that the role of XPC is not limited to NER, but is also implicated in </span>DNA damage response<span><span> (DDR), as well as in cell fate decisions upon stress. Moreover, XPC has a proteolytic role through its interaction with p53 and casp-2S. XPC is also able to determine cellular outcomes through its interaction with downstream proteins, such as p21, ARF, and </span>p16. XPC interactions with effector proteins may drive cells to various fates such as apoptosis, senescence, or tumorigenesis. In this review, we explore XPC’s involvement in different molecular pathways in the cell and suggest that XPC can be considered not only as a genomic caretaker and gatekeeper but also as a </span></span>tumor suppressor and cellular-fate decision maker. These findings envisage that resistance to cell death, induced by DNA-damaging therapeutics, in highly prevalent </span></span><em>P53</em>-deficent tumors might be overcome through new therapeutic approaches that aim to activate XPC in these tumors. Moreover, this review encourages care providers to consider XPC status in cancer patients before chemotherapy in order to improve the chances of successful treatment and enhance patients’ survival.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108400"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44010716","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":"Recommendations and quality criteria for micronucleus studies with humans","authors":"A. Nersesyan ,&nbsp;M. Kundi ,&nbsp;M. Fenech ,&nbsp;H. Stopper ,&nbsp;J. da Silva ,&nbsp;C. Bolognesi ,&nbsp;M. Mišík ,&nbsp;S. Knasmueller","doi":"10.1016/j.mrrev.2021.108410","DOIUrl":"10.1016/j.mrrev.2021.108410","url":null,"abstract":"<div><p>Micronucleus (MN) analyses in peripheral blood lymphocytes and exfoliated cells from different organs (mouth, nose, bladder and cervix) are at present the most widely used approaches to detect damage of genetic material in humans. MN are extranuclear DNA-containing bodies, which can be identified microscopically. They reflect structural and numerical chromosomal aberrations and are formed as a consequence of exposure to occupational, environmental and lifestyle genotoxins. They are also induced as a consequence of inadequate intake of certain trace elements and vitamins. High MN rates are associated with increased risk of cancer and a range of non-cancer diseases in humans. Furthermore, evidence is accumulating that measurements of MN could be a useful tool for the diagnosis and prognosis of different forms of cancer and other diseases (inflammation, infections, metabolic disorders) and for the assessment of the therapeutic success of medical treatments. Recent reviews of the current state of knowledge suggest that many clinical studies have methodological shortcomings. This could lead to controversial findings and limits their usefulness in defining the impact of exposure concentrations of hazardous chemicals, for the judgment of remediation strategies, for the diagnosis of diseases and for the identification of protective or harmful dietary constituents. This article describes important quality criteria for human MN studies and contains recommendations for acceptable study designs. Important parameters that need more attention include sufficiently large group sizes, adequate duration of intervention studies, the exclusion of confounding factors which may affect the results (sex, age, body mass index, nutrition, etc.), the evaluation of appropriate cell numbers per sample according to established scoring criteria as well as the use of proper stains and adequate statistical analyses.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108410"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46162972","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":"Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review","authors":"Samantha Goodman ,&nbsp;Grace Chappell ,&nbsp;Kathryn Z. Guyton ,&nbsp;Igor P. Pogribny ,&nbsp;Ivan Rusyn","doi":"10.1016/j.mrrev.2021.108408","DOIUrl":"10.1016/j.mrrev.2021.108408","url":null,"abstract":"<div><p><span><span><span>Epigenetic alterations, such as changes in DNA </span>methylation, histones/chromatin structure, </span>nucleosome positioning<span>, and expression of non-coding RNAs, are recognized among key characteristics of carcinogens; they may occur independently or concomitantly with genotoxic effects. While data on genotoxicity are collected through standardized guideline tests, data collected on epigenetic effects is far less uniform. In 2016, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints to better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints. Since then, the number of studies of epigenetic effects of chemicals has nearly doubled. This review stands as an update on epigenetic alterations induced by occupational and environmental human carcinogens that were previously and recently classified as Group 1 by the International Agency for Research on Cancer. We found that the evidence of epigenetic effects remains uneven across agents. Studies of DNA methylation are most abundant, while reports concerning effects on non-coding RNA have increased over the past 5 years. By contrast, mechanistic toxicology studies of histone modifications and chromatin state alterations remain few. We found that most publications of epigenetic effects of carcinogens were studies in exposed humans or human cells. Studies in rodents represent the second most common species used for epigenetic studies in toxicology, </span></span><em>in vivo</em> exposures being the most predominant. Future studies should incorporate dose- and time-dependent study designs and also investigate the persistence of effects following cessation of exposure, considering the dynamic nature of most epigenetic alterations.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108408"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10807813","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":"Recurrent driver mutations in benign tumors","authors":"Carolina Cavalieri Gomes","doi":"10.1016/j.mrrev.2022.108412","DOIUrl":"10.1016/j.mrrev.2022.108412","url":null,"abstract":"<div><p><span>The understanding of the molecular pathogenesis<span><span> of benign tumors<span> may bring essential information to clarify the process of tumorigenesis, and ultimately improve the understanding of events such as malignant transformation<span>. The definition of benign neoplasia is not always straightforward and herein the issues surrounding this concept are discussed. Benign neoplasms share all cancer hallmarks with malignancies, except for metastatic potential<span>. Recently, next-generation sequencing has provided unprecedented opportunities to unravel the genetic basis of benign neoplasms and, so far, we have learned that benign neoplasms are indeed characterized by the presence of </span></span></span></span>genetic mutations<span>, including genes rearrangements. Driver mutations in advanced cancer are those that confer growth advantage, and which have been positively selected during cancer evolution. Herein, some discussion will be brought about this concept in the context of cancer prevention, involving precursor lesions and benign neoplasms. When considering early detection and cancer prevention, a driver mutation should not only be advantageous (</span></span></span><em>i.e.,</em> confer survival advantage), but predisposing (<em>i.e.,</em> promoting a cancer phenotype). By including the benign counterparts of malignant neoplasms in tumor biology studies, it is possible to evaluate the risk posed by a given mutation and to differentiate advantageous from predisposing mutations, further refining the concept of driver mutations. Therefore, the study of benign neoplasms should be encouraged because it provides valuable information on tumorigenesis central for understanding the progression from initiation to malignant transformation.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108412"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42229217","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":"Revisiting the structural features of the xeroderma pigmentosum proteins: Focus on mutations and knowledge gaps","authors":"Bruno César Feltes","doi":"10.1016/j.mrrev.2022.108416","DOIUrl":"10.1016/j.mrrev.2022.108416","url":null,"abstract":"<div><p><span>The nucleotide excision repair pathway is a broadly studied DNA repair mechanism because impairments of its key players, the </span>xeroderma pigmentosum proteins (XPA to XPG), are associated with multiple hereditary diseases. Due to the massive number of novel mutations reported for these proteins and new structural data published every year, proper categorization and discussion of relevant observations is needed to organize this extensive inflow of knowledge. This review aims to revisit the structural data of all XP proteins while updating it with the information developed in of the past six years. Discussions and interpretations of mutation outcomes, mechanisms of action, and knowledge gaps regarding their structures are provided, as well as new perspectives based on recent research.</p></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"789 ","pages":"Article 108416"},"PeriodicalIF":5.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42401128","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}