融合基因分析方法在肿瘤研究中的应用与发展

doi:10.3969/j.issn.1000-8535.2023.08.001

广州医药 ›› 2023, Vol. 54 ›› Issue (8): 1-8.DOI: 10.3969/j.issn.1000-8535.2023.08.001

• 专家综述 • 下一篇

融合基因分析方法在肿瘤研究中的应用与发展

张军炜, 管欣超, 刘韬, 杨巧媛

广州医科大学公共卫生学院（广州 511436）

收稿日期:2023-05-02 出版日期:2023-08-20 发布日期:2023-09-13
通讯作者: 杨巧媛,E-mail：qiaoyuan_yang@gzhmu.edu.cn 杨巧媛广州医科大学公共卫生学院副院长,教授,博士生导师,博士后合作导师,广东省本科与校公共卫生与预防医学专业教学指导委员会委员,广东省高等学校“千百十人才培养工程”省级培养对象、广州市高层次青年后备人才,广东省本科高校质量工程预防医学重点专业学科带头人,广东省《卫生毒理学》一流课程负责人,广东省教育厅公共卫生与预防医学实验教学示范中心负责人; 近年来主持完成国家自然科学基金、教育部产学合作协同育人项目、广东省自然科学基金、广东省普通高校重点领域专项、广东省本科高校教学质量与教学改革工程项目等各级科研教学课题20余项,以通信/第一作者在Oncogene、Iscience、Ecotoxicolgy and Environmental Safety、Carcinogenesis、Toxicological Sciences、《中华肿瘤杂志》《中华医学遗传学》等行业知名杂志发表论文40余篇,获得国家教育部高等学校科学研究优秀成果奖二等奖 1项（第二完成人）和广东省科学技术奖二等奖（第二完成人）,同时指导带领学生团队获得全国大学生公共卫生综合技能大赛、中国毒理学会校园科普大赛、广东大学生预防医学实验技能大赛等多个国家级和省级大学生学科竞赛奖励
基金资助:
国家自然科学基金面上项目（81773385）

Development and application of fusion gene analysis methods in tumors research

ZHANG Junwei, GUAN Xinchao, LIU Tao, YANG Qiaoyuan

School of Public Health,Guangzhou Medical University,Guangzhou 511436,China

Received:2023-05-02 Online:2023-08-20 Published:2023-09-13

摘要/Abstract

摘要： 融合基因是指两个独立基因的编码区首尾相连所形成的且置于同一套调控序列控制的产物,研究表明许多癌症的发生与融合基因存在密切的联系。融合基因可作为癌症治疗的靶点,在癌症诊断及治疗领域中融合基因的研究具有重要意义。部分融合基因驱动癌症的机制已被初步揭示,但是有些真实存在的在肿瘤发生发展过程中有重要意义的融合基因由于工具和实验技术限制还未被发现。因此,对融合基因的分析预测研究方法逐渐成为关注的热点之一。本文探讨了目前常用的关于融合基因的分析工具及方法,为融合基因在癌症中的研究提供思路。

关键词: 融合基因, 分析工具, 检测, 验证

Abstract: Fusion genes are the products of two independent genes whose coding regions are linked and controlled by the same set of regulatory sequences．Studies have shown that many cancers are closely linked to gene fusions．Fusion genes can be used as targets for cancer therapy,and the study of fusion genes is of great importance in cancer diagnosis and treatment．Some of the mechanisms of fusion genes driving cancer have been initially revealed,but there are more fusion genes which are important in the process of tumor development have not been discovered due to the limitation of tools and experimental techniques．Therefore,the analysis and prediction methods of fusion genes are becoming a hot topic of interest．In this paper,we discuss the commonly used analytical tools and methods on fusion genes to provide ideas for the study of fusion genes in cancer．

Key words: fusion gene, analysis tools, detection, identification

张军炜, 管欣超, 刘韬, 杨巧媛. 融合基因分析方法在肿瘤研究中的应用与发展[J]. 广州医药, 2023, 54(8): 1-8.

ZHANG Junwei, GUAN Xinchao, LIU Tao, YANG Qiaoyuan. Development and application of fusion gene analysis methods in tumors research[J]. Guangzhou Medical Journal, 2023, 54(8): 1-8.

参考文献

[1] MITELMAN F,JOHANSSON B,MERTENS F.The impact of translocations and gene fusions on cancer causation[J].Nature reviews.Cancer,2007,7(4):233-245.
[2] ROWLEY J D.Letter:A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining[J].Nature,1973,243(5405):290-293.
[3] OSMAN A E G,DEININGER M W.Chronic Myeloid Leukemia:Modern therapies,current challenges and future directions[J].Blood Rev,2021,49:100825.
[4] CHAPMAN A M,SUN K Y,RUESTOW P,et al.Lung cancer mutation profile of EGFR,ALK,and KRAS:Meta-analysis and comparison of never and ever smokers[J].Lung Cancer,2016(102),122-134.
[5] TOGNON C,KNEZEVICH S R,HUNTSMAN D,et al.Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma[J].Cancer cell,2002,2(5):367-376.
[6] SALVATORE D,SANTORO M,SCHLUMBERGER M.The importance of the RET gene in thyroid cancer and therapeutic implications[J].Nature reviews Endocrinology,2021,17(5):296-306.
[7] GARCÍA-PERDOMO H A,CHAVES M J,OSORIO J C,et al.Association between TMPRSS2:ERG fusion gene and the prostate cancer:systematic review and meta-analysis[J].Cent European J Urol,2018,71(4):410-419.
[8] DE BRAEKELEER E,DOUET-GUILBERT N,DE BRAEKELEER M.RARA fusion genes in acute promyelocytic leukemia:a review[J].Expert Rev Hematol,2014,7(3):347-357.
[9] JIANG T,WANG G,LIU Y,et al.Development of small-molecule tropomyosin receptor kinase(TRK)inhibitors for NTRK fusion cancers[J].Acta Pharm Sin B,2021,11(2):355-372.
[10] GABERT J,BEILLARD E,van der VELDEN V H J,et al.Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia - a Europe Against Cancer program[J].Leukemia,2003,17(12):2318-2357.
[11] WANG J,DEAN D C,HORNICEK F J,et al.RNA sequencing(RNA-Seq)and its application in ovarian cancer[J].Gynecol Oncol,2019,152(1):194-201.
[12] BRUNO R,FONTANINI G.Next generation sequencing for gene fusion analysis in lung cancer:a literature review[J].Diagnostics(Basel,Switzerland),2020,10(8):521.
[13] GUPTA S K,JEA J D,YEN L.Validating gene fusion as the source of chimeric RNAs[J].Methods in Mol Biol,2020(2079):187-207.
[14] HEISTERKAMP N,STAM K,GROFFEN J,et al.Structural organization of the bcr gene and its role in the Ph’ translocation[J].Nature,1985,315(6022):758-761.
[15] SARFATY M,MOORE A,NEIMAN V,et al.RET fusion lung carcinoma:Response to therapy and clinical features in a case series of 14 Patients[J].Clin lung Cancer,2017,18(4):e223-e232.
[16] KATAYAMA R,LOVLY C M,SHAW A T.Therapeutic targeting of anaplastic lymphoma kinase in lung cancer:a paradigm for precision cancer medicine[J].Clin Cancer Res,2015,21(10):2227-2235.
[17] BABIN L,ANDRAOS E,FUCHS S,et al.From circRNAs to fusion circRNAs in hematological malignancies[J].JCI Insight,2021,6(21):e151513.
[18] WU K,LIAO X,GONG Y,et al.Circular RNA F-circSR derived from SLC34A2-ROS1 fusion gene promotes cell migration in non-small cell lung cancer[J].Mol Cancer,2019,18(1):98.
[19] GUARNERIO J,BEZZI M,JEONG J C,et al.Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations[J].Cell,2016,165(2):289-302.
[20] FRENKEL-MORGENSTERN M.Identification of chimeric rnas using RNA-Seq reads and protein-protein interactions of translated chimeras[J].Methods Mol Biol,2020(2079):27-40.
[21] MAHER C A,KUMAR-SINHA C,CAO X,et al.Transcriptome sequencing to detect gene fusions in cancer[J].Nature,2009,458(7234):97-101.
[22] JIA W,QIU K,HE M,et al.SOAPfuse:an algorithm for identifying fusion transcripts from paired-end RNA-Seq data[J].Genome Biol,2013,14(2):R12.
[23] VU T N,DENG W,TRAC Q T,et al.A fast detection of fusion genes from paired-end RNA-seq data[J].BMC Genomics,2018,19(1):786.
[24] LIU Z,CHEN X,ROBERTS R,et al.Unraveling gene fusions for drug repositioning in high-risk neuroblastoma[J].Front Pharmacol,2021(12):608778.
[25] LIU S,TSAI W,DING Y,et al.Comprehensive evaluation of fusion transcript detection algorithms and a meta-caller to combine top performing methods in paired-end RNA-seq data[J].Nucleic Acids Res,2016,44(5):e47.
[26] OKONECHNIKOV K,IMAI-MATSUSHIMA A,PAUL L,et al.InFusion:Advancing discovery of fusion genes and chimeric transcripts from deep RNA-sequencing data[J].PLOS ONE,2016,11(12):e167417.
[27] HAAS B J,DOBIN A,STRANSKY N,et al.STAR-Fusion:Fast and Accurate Fusion Transcript Detection from RNA-Seq[DB].bioRxiv,2017:120295.http://repositary.cshl.edu/id/eprint/40278
[28] HAAS B J,DOBIN A,LI B,et al.Accuracy assessment of fusion transcript detection via read-mapping and de novo fusion transcript assembly-based methods[J].Genome Biol,2019,20(1):213.
[29] DAVIDSON N M,MAJEWSKI I J,OSHLACK A.JAFFA:High sensitivity transcriptome-focused fusion gene detection[J].Genome Med,2015,7(1):43.
[30] LAHAYE S,VOYTOVICH K,FITCH J,et al.Utilization of an ensemble approach for identification of driver fusions in pediatric cancer[C].Proceedings:AACR Annual Meeting 2019,2019.
[31] UHRIG S,ELLERMANN J,WALTHER T,et al.Accurate and efficient detection of gene fusions from RNA sequencing data[J].Genome Res,2021,31(3):448-460.
[32] STICHEL D,SCHRIMPF D,CASALINI B,et al.Routine RNA sequencing of formalin-fixed paraffin-embedded specimens in neuropathology diagnostics identifies diagnostically and therapeutically relevant gene fusions[J].Acta Neuropathol,2019,138(5):827-835.
[33] KERBS P,VOSBERG S,KREBS S,et al.Fusion gene detection by RNA-sequencing complements diagnostics of acute myeloid leukemia and identifies recurring NRIP1-MIR99AHG rearrangements[J].Haematologica,2022,107(1):100-111.
[34] CAI Z,XUE H,XU Y,et al.Fcirc:A comprehensive pipeline for the exploration of fusion linear and circular RNAs[J].Gigascience,2020,9(6):giaa054.
[35] KIM C,NA K,PARK S,et al.FusionPro,a versatile proteogenomic tool for identification of novel fusion transcripts and their potential translation products in cancer cells[J].Mol Cell Proteomics,2019,18(8):1651-1668.
[36] WEBER D,IBN-SALEM J,SORN P,et al.Accurate detection of tumor-specific gene fusions reveals strongly immunogenic personal neo-antigens[J].Nature Biotechnol,2022,40(8):1276-1284.
[37] KIM P,TAN H,LIU J,et al.FusionAI:Predicting fusion breakpoint from DNA sequence with deep learning[J].iScience,2021,24(10):103164.
[38] KIM P,TAN H,LIU J,et al.FusionAI,a DNA-sequence-based deep learning protocol reduces the false positives of human fusion gene prediction[J].STAR Protoc,2022,3(1):101185.
[39] LOVINO M,MONTEMURRO M,BARRESE V S,et al.Identifying the oncogenic potential of gene fusions exploiting miRNAs.[J].J Biomed Inform,2022(129):104057.
[40] FILIPOWICZ W,BHATTACHARYYA S N,SONENBERG N.Mechanisms of post-transcriptional regulation by microRNAs:are the answers in sight?[J].Nat Rev Genet,2008,9(2):102-114.
[41] LYU X,WANG X,ZHANG L,et al.Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay[J].Diagn Pathol,2017,12(1):55.
[42] 梁小芹,王玲,刘凤磊,等.免疫组织化学和荧光原位杂交检测肺腺癌ROS1表达的对比[J].临床与实验病理学杂志,2016,32(8):882-886.
[43] VAN BOCKSTAL M R,BENIUGA G,CRACIUN L,et al.The use of pan-tropomyosin receptor kinase immunohistochemistry as a screening tool for the detection of neurotrophic tropomyosin-related kinase fusions:Real-World Data from a national multicentric retrospective study[J].Pathobiology,2022,89(6):393-406.
[44] XU B,AL RASHEED M R H,ANTONESCU C R,et al.Pan-Trk immunohistochemistry is a sensitive and specific ancillary tool for diagnosing secretory carcinoma of the salivary gland and detecting ETV6-NTRK3 fusion[J].Histopathology,2020,76(3):375-382.
[45] 王玉鹏. 基因选择性剪接位点鉴定与预测方法研究[D].南京:南京林业大学,2021.
[46] 赵静,林丽梅.基于分子网络的疾病基因预测方法综述[J].电子科技大学学报,2017,46(5):755-765.
[47] 张宁芮. 基于异构网络的疾病基因识别方法研究[D].乌鲁木齐:新疆大学,2021.
[48] XING Z,CHU C,CHEN L,et al.The use of Gene Ontology terms and KEGG pathways for analysis and prediction of oncogenes.[J].Biochim Biophys Acta,2016,1860(11 Pt B):2725-2734.

融合基因分析方法在肿瘤研究中的应用与发展

Development and application of fusion gene analysis methods in tumors research

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 10

编辑推荐

Metrics

本文评价

[1]	陈运恒, 邱莉, 廖翠芳, 骆红. 河源市源城区2 468例儿童呼吸道感染病原体核酸检测结果分析[J]. 广州医药, 2023, 54(8): 17-21.
[2]	高磊, 赵梅, 高文杰. 献血者HBV核酸检测非重复反应性确认及追踪结果分析[J]. 广州医药, 2021, 52(5): 83-87.
[3]	李月菊. HPV联合TCT检测对宫颈病变诊断的预测价值[J]. 广州医药, 2021, 52(3): 48-51.
[4]	陈红霞. ELISA联合NAT技术在献血者血液筛查和输血残余风险分析中的应用[J]. 广州医药, 2020, 51(6): 117-119.
[5]	张霞, 刘新刚, 徐刚, 覃文琪, 李阿丽, 郑卫东. 融合基因阳性急性B淋巴细胞白血病患儿免疫表型分析[J]. 广州医药, 2020, 51(2): 40-44.
[6]	朱素优. 无创产前基因检测技术在胎儿染色体非整倍体疾病诊断中的检出效率及临床应用价值[J]. 广州医药, 2018, 49(6): 79-82.
[7]	曾聪灵. 血清过敏原检测在小儿过敏性紫癜中的临床价值[J]. 广州医药, 2018, 49(6): 101-103.
[8]	张敏, 徐英. 直接面向消费者的基因检测相关需求分析[J]. 广州医药, 2018, 49(5): 98-103.
[9]	聂湘辉, 刘丽华, 胡莅鸿. ChiTaS BSS1200血液核酸检测系统的分析性能验证[J]. 广州医药, 2016, 47(4): 68-69.
[10]	岑美婷, 陈纯旭, 吴振兴, 张慧. 儿童化学发光免疫检测中的稀释方法研究[J]. 广州医药, 2016, 47(1): 59-61.