Global Medical Genetics最新文献

{"title":"Genomic Landscape Features of Minimally Invasive Adenocarcinoma and Invasive Lung Adenocarcinoma.","authors":"Wei Zhang, Hui Xu, Ning Tang, Shuang Han, Hongyan Shu","doi":"10.1055/s-0044-1791198","DOIUrl":"10.1055/s-0044-1791198","url":null,"abstract":"<p><p><b>Background</b>  The widespread implementation of computed tomography has significantly increased the detection of small pulmonary nodules, including atypical adenomatous hyperplasia, minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC). Few studies have focused on the genomic differences between MIA and IAC. <b>Methods</b>  We retrospectively analyzed patients with lung adenocarcinoma (LUAD) who underwent surgery from January 2020 to December 2023. Patients were categorized into MIA and IAC groups. The mutation status of common driver genes was assessed using next-generation sequencing. <b>Results</b>  A total of 422 LUAD patients were included in the study, comprising 119 MIA cases and 303 IAC cases. MIA patients were younger and predominantly female compared with IAC patients. EGFR mutations were detected in 251 patients (59.5%), with the frequency of EGFR mutations increasing from 37.0% in MIA to 68.3% in IAC ( <i>p</i>  < 0.001). TP53 mutations were found in 108 patients (25.6%), with 7 patients (5.9%) in MIA and 101 patients (33.3%) in IAC ( <i>p</i>  < 0.001). ERBB2 mutations were identified in 23 MIA patients (19.3%) and 20 IAC patients (6.6%) ( <i>p</i>  < 0.001). Additionally, CDKN2A mutations were detected in 23 IAC patients (7.6%), while no mutations in this gene were found in the MIA group. Moreover, ALK and RET gene fusions were identified in 11 patients, respectively. <b>Conclusion</b>  ERBB2 mutations and RET fusions are early genomic events in LUAD, while TP53 and CDKN2A mutations and ALK fusions occur later. Genomic intratumor heterogeneity likely arises early, before invasive characteristics develop.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"312-318"},"PeriodicalIF":1.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Genome Editing Tools and Their Application on Genetic Inheritance Disorders.","authors":"Dae Hwan Oh","doi":"10.1055/s-0044-1790558","DOIUrl":"10.1055/s-0044-1790558","url":null,"abstract":"<p><p>In the fields of medicine and bioscience, gene editing is increasingly recognized as a promising therapeutic approach for treating pathogenic variants in humans and other living organisms. With advancements in technology and knowledge, it is now understood that most genetic defects are caused by single-base pair variants. The ability to substitute genes using genome editing tools enables scientists and doctors to cure genetic diseases and disorders. Starting with CRISPR (clustered regularly interspaced short palindromic repeats)/Cas, the technology has evolved to become more efficient and safer, leading to the development of base and prime editors. Furthermore, various approaches are used to treat genetic disorders such as hemophilia, cystic fibrosis, and Duchenne muscular dystrophy. As previously mentioned, most genetic defects leading to specific diseases are caused by single-base pair variants, which can occur at many locations in corresponding gene, potentially causing the same disease. This means that, even when using the same genome editing tool, results in terms of editing efficiency or treatment effectiveness may differ. Therefore, different approaches may need to be applied to different types of diseases. Prevalently, due to the safety of adeno-associated virus (AAV) vectors in gene therapy, most clinical trials of gene therapy are based on AAV delivery methods. However, despite their safety and nonintegration into the host genome, their limitations, such as confined capacity, dosage-dependent viral toxicity, and immunogenicity, necessitate the development of new approaches to enhance treatment effects. This review provides the structure and function of each CRISPR-based gene editing tool and focuses on introducing new approaches in gene therapy associated with improving treatment efficiency.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"319-329"},"PeriodicalIF":1.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert Consensus on the Diagnosis and Treatment of FGFR Gene-Altered Solid Tumors.","authors":"Chunwei Xu, Bin Lian, Juanjuan Ou, Qian Wang, Wenxian Wang, Ke Wang, Dong Wang, Zhengbo Song, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Lili Mao, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Xiaoyan Li, Chuanhao Tang, Chengzhi Zhou, Junping Zhang, Junli Xue, Hui Guo, Qian Chu, Rui Meng, Jingxun Wu, Rui Zhang, Jin Zhou, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Yuanyuan Lu, Xiaofeng Chen, Rui Ge, Enyong Dai, Yu Han, Weiwei Pan, Fei Pang, Jintao Huang, Kai Wang, Fan Wu, Bingwei Xu, Liping Wang, Youcai Zhu, Li Lin, Yanru Xie, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Pingli Sun, Hong Wang, Mingxiang Ye, Zhaofeng Wang, Yue Hao, Zhen Wang, Bin Wan, Donglai Lv, Zhanqiang Zhai, Shengjie Yang, Jing Kang, Jiatao Zhang, Chao Zhang, Lin Shi, Yina Wang, Bihui Li, Zhang Zhang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Huijuan Wang, Gu Jin, Guansong Wang, Jiandong Wang, Meiyu Fang, Yong Fang, Yuan Li, Xiaojia Wang, Jing Chen, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Biyun Wang, Lu Si, Yuanzhi Lu, Ziming Li, Wenfeng Fang, Yong Song","doi":"10.1055/s-0044-1790230","DOIUrl":"10.1055/s-0044-1790230","url":null,"abstract":"<p><p>The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"330-343"},"PeriodicalIF":1.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11405117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Noncoding RNAs in Modulating Microglial Phenotype.","authors":"Eiman Meer","doi":"10.1055/s-0044-1790283","DOIUrl":"10.1055/s-0044-1790283","url":null,"abstract":"<p><p>Microglia are immunocompetent cells that are present in the retina and central nervous system, and are involved in the development maintenance and immune functions in these systems. Developing from yolk sac-primitive macrophages, they proliferate in the local tissues during the embryonic period without resorting to the production from the hematopoietic stem cells, and are critical in sustaining homeostasis and performing in disease and injury; they have morphological characteristics and distinct phenotypes according to the microenvironment. Microglia are also present in close association with resident cells in the retina where they engage in synapse formation, support normal functions, as well as immune defense. They are involved in the development of numerous neurodegenerative and ophthalmic diseases and act as diversity shields and triggers. Noncoding ribonucleic acids (ncRNAs) refer to RNA molecules synthesized from the mammalian genome, and these do not have protein-coding capacity. These ncRNAs play a role in the regulation of gene expression patterns. ncRNAs have only been recently identified as vastly significant molecules that are involved in the posttranscriptional regulation. Microglia are crucial for brain health and functions and current studies have focused on the effects caused by ncRNA on microglial types. Thus, the aim of the review was to provide an overview of the current knowledge about the regulation of microglial phenotypes by ncRNAs.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"304-311"},"PeriodicalIF":1.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11383642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic Heterogeneity in ORAI-1-Associated Congenital Myopathy.","authors":"Dipti Baskar, Seena Vengalil, Kiran Polavarapu, Veeramani Preethish-Kumar, Gautham Arunachal, Ramya Sukrutha, Mainak Bardhan, Akshata Huddar, Gopikrishnan Unnikrishnan, Girish Baburao Kulkarni, Yasha T Chickabasaviah, Rashmi Santhosh Kumar, Atchayaram Nalini, Saraswati Nashi","doi":"10.1055/s-0044-1790245","DOIUrl":"10.1055/s-0044-1790245","url":null,"abstract":"<p><p><b>Introduction</b>  ORAI-1 is a plasma membrane calcium release-activated calcium channel that plays a crucial role in the excitation-contraction of skeletal muscles. Loss-of-function mutations of <i>ORAI-1</i> cause severe combined immunodeficiency, nonprogressive muscle hypotonia, and anhidrotic ectodermal dysplasia. Autosomal dominant gain-of-function mutation causes Stormorken's syndrome, which includes tubular aggregate myopathy along with bleeding diathesis. <b>Methods</b>  This is a description of a genetically confirmed case of ORAI-1-associated myopathy with clinical, histopathological, and imaging characteristics and a detailed literature review. <b>Results</b>  We report an 18-year-old woman who presented with 2-and-a-half year history of slowly progressive proximal lower limb weakness and ophthalmoparesis. Her serum creatine kinase levels were normal. Magnetic resonance imaging of the muscle showed predominant fatty infiltration of the glutei and quadriceps femoris. Histopathological analysis of muscle biopsy was suggestive of congenital fiber-type disproportion (CFTD). Clinical exome sequencing showed novel homozygous nonsense pathogenic variant NC_000012.12 (NM_032790.3): c.205G > T (p.Glu69Ter) in <i>ORAI-1</i> gene. <b>Conclusion</b>  This report expands the phenotypic spectrum of ORAI-1-related myopathy to include congenital myopathy-CFTD with ophthalmoparesis, a novel manifestation.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"297-303"},"PeriodicalIF":1.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Mechanism and Perspectives of Mesenchymal Stem Cell Therapy for Ischemic Stroke: A Review.","authors":"Pengcheng Zhu, Hongtu Tan, Haobo Gao, Jiabin Wang, Yangyang Liu, Dongyi Yang, Tao Wu","doi":"10.1055/s-0044-1790231","DOIUrl":"10.1055/s-0044-1790231","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Research have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of MSCs in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"278-284"},"PeriodicalIF":1.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Viral Oncoproteins and Ubiquitin-Proteasome System.","authors":"Zahra Rafiei Atani, Sareh Sadat Hosseini, Hossein Goudarzi, Ebrahim Faghihloo","doi":"10.1055/s-0044-1790210","DOIUrl":"10.1055/s-0044-1790210","url":null,"abstract":"<p><p>Some human cancers worldwide may be related to human tumor viruses. Knowing, controlling, and managing the viruses that cause cancers remain a problem. Also, tumor viruses use ubiquitin-proteasome system (UPS) that can alter host cellular processes through UPS. Human tumor viruses cause persistent infections, due to their ability to infect their host cells without killing them. Tumor viruses such as Epstein-Barr virus, hepatitis C virus, hepatitis B virus, human papillomaviruses, human T cell leukemia virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus are associated with human malignancies. They interfere with the regulation of cell cycle and control of apoptosis, which are important for cellular functions. These viral oncoproteins bind directly or indirectly to the components of UPS, modifying cellular pathways and suppressor proteins like p53 and pRb. They can also cause progression of malignancy. In this review, we focused on how viral oncoproteins bind to the components of the UPS and how these interactions induce the degradation of cellular proteins for their survival.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"285-296"},"PeriodicalIF":1.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically Predicted Iron Status Is a Causal Risk of Rheumatoid Arthritis: A Mendelian Randomization Study.","authors":"Boyuan Wu","doi":"10.1055/s-0044-1789259","DOIUrl":"10.1055/s-0044-1789259","url":null,"abstract":"<p><p><b>Background</b>  Current knowledge on iron's role in rheumatoid arthritis (RA) development is very limited, with studies yielding inconsistent findings. We conducted a two-sample Mendelian randomization study to assess the associations of iron status with the risk of RA. <b>Methods</b>  This study leveraged genetic data from a large genome-wide association study (GWAS) of 257,953 individuals to identify single nucleotide polymorphisms (SNPs) associated with iron status. We then analyzed these data in conjunction with summary-level data on RA from the IEU open GWAS project, which included 5,427 RA cases and 479,171 controls. An inverse-variance weighted method with random effects was employed, along with sensitivity analyses, to assess the relationship between iron status and RA risk. <b>Results</b>  Genetic predisposition to high ferritin and serum iron status was causally associated with lower odds of RA. Ferritin had an odds ratio (OR) of 0.997 (95% confidence interval [CI]: 0.995-0.997; <i>p</i>  = 0.010), indicating that a one-unit increase in ferritin is associated with a 0.3% decrease in the odds of RA. Similarly, serum iron had an OR of 0.997 (95% CI: 0.995-0.999; <i>p</i>  = 0.014). However, MR analyses found no significant causal associations between total iron-binding capacity (OR = 1.0, 95% CI: 0.999-1.002; <i>p</i>  = 0.592) or transferrin saturation percentage (OR = 0.998, 95% CI: 0.996-1.000; <i>p</i>  = 0.080) and risk of developing RA. <b>Conclusions</b>  This study suggests that individuals with genes linked to higher iron levels may have a lower risk of developing RA. Our findings indicate that the total amount of iron in the body, rather than how it is distributed, might be more important for RA. This raises the intriguing possibility that iron supplementation could be a preventative strategy, but further research is necessary.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"270-277"},"PeriodicalIF":1.5,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"16S rRNA Sequencing Reveals Alterations of Gut Bacteria in Hirschsprung-Associated Enterocolitis.","authors":"Hao Shi, Yong She, Wu Mao, Yi Xiang, Lu Xu, Sanjun Yin, Qi Zhao","doi":"10.1055/s-0044-1789237","DOIUrl":"10.1055/s-0044-1789237","url":null,"abstract":"<p><p>Hirschsprung-associated enterocolitis (HAEC) stands as most common and serious complication of Hirschsprung's disease. Variations in the microbiota composition may account for the differences observed between HAEC and healthy individuals, offering crucial insights into the disease's pathogenesis. Here, we performed a study to changes in the gut microbiome using 16sRNA amplicon sequencing in a cohort of HAEC patients ( <i>n</i>  = 16) and healthy controls ( <i>n</i>  = 14). Our result revealed a significant disparity in beta diversity between the two groups. Following correction for false discovery rate, a rank-sum test at the genus level indicated a notable decrease in the relative abundance of <i>Bifidobacterium</i> , <i>Lactobacillus</i> , and <i>Veillonella</i> , whereas the <i>Enterococcus</i> genus exhibited a substantial increase in HAEC, a finding further supported by additional linear discriminant analysis effect size analysis. Functional analysis showed that putative transport and catabolism, digestive system, and metabolism of cofactors and vitamins were proved to be some abundant KOs (Kyoto Encyclopedia of Genes and Genomes [KEGG] orthologs) in healthy group, whereas infectious disease, membrane transport, and carbohydrate metabolism were the three KOs with the higher abundance in the HAEC group. Our data increased our insight into the HAEC, which may shed further light on HAEC pathogenesis. Our study firstly demonstrated the difference between fecal microbiota of HAEC patients and healthy individuals, which made a step forward in the understanding of the pathophysiology of HAEC.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"263-269"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.","authors":"Lei Cao, Wencong Tian, Yongjie Zhao, Peng Song, Jia Zhao, Chuntao Wang, Yanhong Liu, Hong Fang, Xingqiang Liu","doi":"10.1055/s-0044-1789204","DOIUrl":"10.1055/s-0044-1789204","url":null,"abstract":"<p><p>Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine-threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named \"quadruple WT\" GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.</p>","PeriodicalId":40142,"journal":{"name":"Global Medical Genetics","volume":"11 4","pages":"251-262"},"PeriodicalIF":1.5,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11341198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}