Pub Date : 2025-01-01DOI: 10.1016/j.mrrev.2024.108529
Ran Xu , Mengmeng Zhang , Xiaoming Yang , Weiming Tian , Changyan Li
In recent years, next-generation high-throughput sequencing technology has been widely used in clinical practice for the identification and diagnosis of Mendelian diseases as an auxiliary detection method. Nevertheless, due to the limitations in read length and poor coverage of complex genomic regions, the etiology of many genetic diseases is unclear. Long-read sequencing (LRS) addresses these limitations of next-generation sequencing. LRS is an effective tool for the clinical study of the etiology of complex genetic diseases. In this review, we summarized the current research on the application of LRS in diseases across various systems. We also reported the improvements in the diagnostic rate and common variant types of LRS in different studies, providing a foundation for the discovery of new disease mechanisms, which is anticipated to play a crucial role in future research on genetic diseases.
{"title":"Decoding complexity: The role of long-read sequencing in unraveling genetic disease etiologies","authors":"Ran Xu , Mengmeng Zhang , Xiaoming Yang , Weiming Tian , Changyan Li","doi":"10.1016/j.mrrev.2024.108529","DOIUrl":"10.1016/j.mrrev.2024.108529","url":null,"abstract":"<div><div>In recent years, next-generation high-throughput sequencing technology has been widely used in clinical practice for the identification and diagnosis of Mendelian diseases as an auxiliary detection method. Nevertheless, due to the limitations in read length and poor coverage of complex genomic regions, the etiology of many genetic diseases is unclear. Long-read sequencing (LRS) addresses these limitations of next-generation sequencing. LRS is an effective tool for the clinical study of the etiology of complex genetic diseases. In this review, we summarized the current research on the application of LRS in diseases across various systems. We also reported the improvements in the diagnostic rate and common variant types of LRS in different studies, providing a foundation for the discovery of new disease mechanisms, which is anticipated to play a crucial role in future research on genetic diseases.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108529"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957841","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}
Pub Date : 2025-01-01DOI: 10.1016/j.mrrev.2025.108536
Jing Liu, Zheng Wang
Glioblastoma (GBM) is a lethal central nervous system tumor, characterized by extensive genomic alterations and high intra-tumoral heterogeneity. Gene fusions, derived from chromosomal translocations, deletions, and inversions, were increasingly recognized as key carcinogenic events, with the highest frequency of FGFR-TACC fusion in glioblastoma. As reported, FGFR3-TACC3 fusion mostly coexists with wild-type IDH status, and associates with better prognosis. Mechanistically, FGFR3-TACC3 fusions can constitutively activate non-canonical FGFR downstream pathways, induce aneuploidy, and participate in mitochondrial metabolism, thereby promoting cell proliferation and tumorigenesis. These functions, whether based on FGFR3 phosphorylation or not, are predominantly attributed to the specific domain of TACC3 that involved in regulating the localization and activation of fusion products. Several preclinical studies and clinical trials are being performed to evaluate the efficacy and safety of the FGFR-TACC fusion as a personalised therapeutic target, including the treatments with tyrosine kinase inhibitors, metabolic inhibitors, HSP90 inhibitors, coiled-coil peptide-mimetics, and targeted protein degraders. A subset of populations with FGFR-TACC-positive glioblastoma, after refined molecular screening strategies, may benefit from targeted therapies. Despite major progress in biotechnology, our understanding on the role of fusion events in glioblastoma represented by the FGFR-TACC is still in its infancy. Here, we highlight recent progress on FGFR-TACC fusion in human glioblastoma, emphasizing their molecular mechanisms and potential clinical value.
{"title":"The landscape of FGFR-TACC fusion in adult glioblastoma: From bench to bedside","authors":"Jing Liu, Zheng Wang","doi":"10.1016/j.mrrev.2025.108536","DOIUrl":"10.1016/j.mrrev.2025.108536","url":null,"abstract":"<div><div>Glioblastoma (GBM) is a lethal central nervous system tumor, characterized by extensive genomic alterations and high intra-tumoral heterogeneity. Gene fusions, derived from chromosomal translocations, deletions, and inversions, were increasingly recognized as key carcinogenic events, with the highest frequency of FGFR-TACC fusion in glioblastoma. As reported, FGFR3-TACC3 fusion mostly coexists with wild-type IDH status, and associates with better prognosis. Mechanistically, FGFR3-TACC3 fusions can constitutively activate non-canonical FGFR downstream pathways, induce aneuploidy, and participate in mitochondrial metabolism, thereby promoting cell proliferation and tumorigenesis. These functions, whether based on FGFR3 phosphorylation or not, are predominantly attributed to the specific domain of TACC3 that involved in regulating the localization and activation of fusion products. Several preclinical studies and clinical trials are being performed to evaluate the efficacy and safety of the FGFR-TACC fusion as a personalised therapeutic target, including the treatments with tyrosine kinase inhibitors, metabolic inhibitors, HSP90 inhibitors, coiled-coil peptide-mimetics, and targeted protein degraders. A subset of populations with FGFR-TACC-positive glioblastoma, after refined molecular screening strategies, may benefit from targeted therapies. Despite major progress in biotechnology, our understanding on the role of fusion events in glioblastoma represented by the FGFR-TACC is still in its infancy. Here, we highlight recent progress on FGFR-TACC fusion in human glioblastoma, emphasizing their molecular mechanisms and potential clinical value.</div></div>","PeriodicalId":49789,"journal":{"name":"Mutation Research-Reviews in Mutation Research","volume":"795 ","pages":"Article 108536"},"PeriodicalIF":6.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850296","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}
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IF 4.2 2区 医学Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
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