{"entity":{"id":"gene-fusion","kind":"term","name":"Gene fusion","aka":["gene fusions","fusion gene","fusion genes","fusion-driven","fusion-positive","fusions","oncogenic fusions","rearrangement","chromosomal translocation","chromosomal rearrangements"],"tldr":"A gene fusion is two genes broken and joined together, creating a hybrid protein that can drive cancer. Fusion-driven cancers are often exquisitely drug-sensitive.","summary":"A gene fusion joins two broken genes into one, producing a hybrid protein that can drive cancer, and fusion-driven cancers are often exquisitely drug-sensitive. Well-known examples include EML4-ALK, ROS1, RET, NTRK, FGFR2, NRG1 and BCR-ABL, and the ALK, RET, NTRK and FGFR2 targets are linked here. Fusions are best detected by RNA sequencing & expression profiling, define tumour-agnostic indications for NTRK and RET, and are the archetype of oncogene addiction. The term is cited by the Biliary tract cancer and Ewing sarcoma entries, by FGFR2 fusions and rearrangements, by Janet Rowley, Arul M. Chinnaiyan and Olivier Delattre, and by ideas on degraders for the fusion proteins that drive childhood sarcomas and a standard for tumour-agnostic approvals.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fusion_gene","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fusion_gene"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["rna-seq"],"targets":["alk","ret","ntrk","fgfr2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-soda-eml4-alk-fusion-nature-2007","paper-bergethon-ros1-rearrangements-lung-jco-2012","paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":[],"dependsOn":[],"notes":["Lung cancer carries five licensed fusion targets (ALK 3 to 6%, ROS1 1 to 3%, RET 1 to 2%, NTRK about 0.2%, NRG1 about 0.3%) and they share a testing problem: a DNA panel finds a rearrangement only where it baits the intron the break falls in, so panel rates run below fluorescence in situ hybridisation rates and RNA-based rates, and partners are heterogeneous enough in NRG1 that named-fusion assays miss most of them (Kris 2014, Jonna 2019). Point mutations in the same genes read 2 to 8% on exome panels and are passengers. The practical rule is that a driver-negative adenocarcinoma, especially in a never smoker, has not been fully tested until a fusion-capable assay has been run (Lindeman 2018)."],"category":"Genomics & genetics"},"route":"/terms/gene-fusion/","neighbours":{"cancer":[{"id":"alk-positive-nsclc","kind":"cancer","name":"ALK-positive non-small-cell lung cancer","route":"/cancers/alk-positive-nsclc/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"ewing-sarcoma","kind":"cancer","name":"Ewing sarcoma","route":"/cancers/ewing-sarcoma/"},{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","route":"/cancers/inflammatory-myofibroblastic-tumour/"},{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"ntrk-fusion-nsclc","kind":"cancer","name":"NTRK fusion-positive non-small-cell lung cancer","route":"/cancers/ntrk-fusion-nsclc/"},{"id":"nut-carcinoma","kind":"cancer","name":"NUT carcinoma (midline carcinoma with NUTM1 rearrangement)","route":"/cancers/nut-carcinoma/"},{"id":"pancreatic-acinar-cell-carcinoma","kind":"cancer","name":"Pancreatic acinar cell carcinoma","route":"/cancers/pancreatic-acinar-cell-carcinoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"ret-fusion-nsclc","kind":"cancer","name":"RET fusion-positive non-small-cell lung cancer","route":"/cancers/ret-fusion-nsclc/"},{"id":"rhabdomyosarcoma","kind":"cancer","name":"Rhabdomyosarcoma","route":"/cancers/rhabdomyosarcoma/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"ewsr1-fli1","kind":"target","name":"EWSR1-FLI1 fusion","route":"/targets/ewsr1-fli1/"},{"id":"fgfr2","kind":"target","name":"FGFR2","route":"/targets/fgfr2/"},{"id":"nrg1","kind":"target","name":"NRG1","route":"/targets/nrg1/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"},{"id":"rspo2","kind":"target","name":"RSPO2","route":"/targets/rspo2/"},{"id":"rspo3","kind":"target","name":"RSPO3","route":"/targets/rspo3/"}],"paper":[{"id":"paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","kind":"paper","name":"ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer","route":"/key-papers/paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019/"},{"id":"paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014","kind":"paper","name":"CD74-NRG1 fusions in lung adenocarcinoma","route":"/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/"},{"id":"paper-jonna-nrg1-fusions-solid-tumours-ccr-2019","kind":"paper","name":"Detection of NRG1 gene fusions in solid tumors","route":"/key-papers/paper-jonna-nrg1-fusions-solid-tumours-ccr-2019/"},{"id":"paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012","kind":"paper","name":"Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer","route":"/key-papers/paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012/"},{"id":"paper-shaw-crown-lorlatinib-crizotinib-nejm-2020","kind":"paper","name":"First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer","route":"/key-papers/paper-shaw-crown-lorlatinib-crizotinib-nejm-2020/"},{"id":"paper-nakamura-biliary-genomic-spectra-nat-genet-2015","kind":"paper","name":"Genomic spectra of biliary tract cancer","route":"/key-papers/paper-nakamura-biliary-genomic-spectra-nat-genet-2015/"},{"id":"paper-soda-eml4-alk-fusion-nature-2007","kind":"paper","name":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","route":"/key-papers/paper-soda-eml4-alk-fusion-nature-2007/"},{"id":"paper-taylor-integrative-genomic-profiling-cancer-cell-2010","kind":"paper","name":"Integrative genomic profiling of human prostate cancer","route":"/key-papers/paper-taylor-integrative-genomic-profiling-cancer-cell-2010/"},{"id":"paper-gainor-alk-resistance-mutations-cancer-discov-2016","kind":"paper","name":"Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer","route":"/key-papers/paper-gainor-alk-resistance-mutations-cancer-discov-2016/"},{"id":"paper-tomlins-tmprss2-ets-fusion-science-2005","kind":"paper","name":"Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer","route":"/key-papers/paper-tomlins-tmprss2-ets-fusion-science-2005/"},{"id":"paper-seshagiri-rspo-fusions-colon-nature-2012","kind":"paper","name":"Recurrent R-spondin fusions in colon cancer","route":"/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/"},{"id":"paper-bergethon-ros1-rearrangements-lung-jco-2012","kind":"paper","name":"ROS1 rearrangements define a unique molecular class of lung cancers","route":"/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/"},{"id":"paper-tcga-molecular-taxonomy-primary-prostate-cell-2015","kind":"paper","name":"TCGA: the molecular taxonomy of primary prostate cancer","route":"/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/"},{"id":"paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018","kind":"paper","name":"The long tail of oncogenic drivers in prostate cancer","route":"/key-papers/paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018/"},{"id":"paper-grasso-mutational-landscape-lethal-crpc-nature-2012","kind":"paper","name":"The mutational landscape of lethal castration-resistant prostate cancer","route":"/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/"},{"id":"paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012","kind":"paper","name":"The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis","route":"/key-papers/paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012/"},{"id":"paper-lindeman-lung-molecular-testing-guideline-jto-2018","kind":"paper","name":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","route":"/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/"},{"id":"paper-ren-chinese-prostate-whole-genome-eur-urol-2018","kind":"paper","name":"Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression","route":"/key-papers/paper-ren-chinese-prostate-whole-genome-eur-urol-2018/"}],"term":[{"id":"chromosome","kind":"term","name":"Chromosome","route":"/terms/chromosome/"},{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","route":"/terms/cytogenetics/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"},{"id":"fgfr2-fusion","kind":"term","name":"FGFR2 fusions and rearrangements","route":"/terms/fgfr2-fusion/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"foxo1-fusion-status","kind":"term","name":"FOXO1 fusion status and IRS group (rhabdomyosarcoma)","route":"/terms/foxo1-fusion-status/"},{"id":"philadelphia-chromosome","kind":"term","name":"Philadelphia chromosome (Ph+, BCR::ABL1)","route":"/terms/philadelphia-chromosome/"},{"id":"sarcoma-type","kind":"term","name":"Sarcoma (tissue type)","route":"/terms/sarcoma-type/"},{"id":"ss18-ssx-fusion","kind":"term","name":"SS18::SSX fusion (synovial sarcoma)","route":"/terms/ss18-ssx-fusion/"},{"id":"lymphoma-bio-germinal-centre","kind":"term","name":"The germinal centre: why lymphoma starts where antibodies are made","route":"/terms/lymphoma-bio-germinal-centre/"}],"biomarker":[{"id":"alk-fusion","kind":"biomarker","name":"ALK fusion (ALK-positive)","route":"/biomarkers/alk-fusion/"},{"id":"alk-resistance-mutation","kind":"biomarker","name":"ALK kinase-domain resistance mutation (G1202R and the rest)","route":"/biomarkers/alk-resistance-mutation/"},{"id":"braf-fusion","kind":"biomarker","name":"BRAF fusion or rearrangement","route":"/biomarkers/braf-fusion/"},{"id":"fgfr2-fusion-rearrangement","kind":"biomarker","name":"FGFR2 fusion or rearrangement","route":"/biomarkers/fgfr2-fusion-rearrangement/"},{"id":"fgfr3-alteration","kind":"biomarker","name":"FGFR3 alteration (mutation or fusion)","route":"/biomarkers/fgfr3-alteration/"},{"id":"nrg1-fusion","kind":"biomarker","name":"NRG1 gene fusion","route":"/biomarkers/nrg1-fusion/"},{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"},{"id":"ret-fusion","kind":"biomarker","name":"RET fusion and RET mutation","route":"/biomarkers/ret-fusion/"},{"id":"ros1-fusion","kind":"biomarker","name":"ROS1 fusion (ROS1-positive)","route":"/biomarkers/ros1-fusion/"},{"id":"spop-mutation","kind":"biomarker","name":"SPOP mutation","route":"/biomarkers/spop-mutation/"},{"id":"tmprss2-erg-fusion","kind":"biomarker","name":"TMPRSS2-ERG fusion (and the other ETS rearrangements)","route":"/biomarkers/tmprss2-erg-fusion/"}],"trial":[{"id":"profile-1001-ros1","kind":"trial","name":"PROFILE 1001 ROS1 expansion cohort","route":"/trials/profile-1001-ros1/"},{"id":"profile-1014","kind":"trial","name":"PROFILE 1014","route":"/trials/profile-1014/"}],"person":[{"id":"arul-chinnaiyan","kind":"person","name":"Arul M. Chinnaiyan","route":"/people/arul-chinnaiyan/"},{"id":"janet-rowley","kind":"person","name":"Janet Rowley","route":"/people/janet-rowley/"},{"id":"olivier-delattre","kind":"person","name":"Olivier Delattre","route":"/people/olivier-delattre/"}],"idea":[{"id":"idea-tr1-tumour-agnostic-approval-standard","kind":"idea","name":"A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling","route":"/ideas/idea-tr1-tumour-agnostic-approval-standard/"},{"id":"idea-bio1-fusion-tf-degraders","kind":"idea","name":"Degraders for the fusion proteins that drive childhood sarcomas","route":"/ideas/idea-bio1-fusion-tf-degraders/"},{"id":"idea-bio2-paediatric-first-development","kind":"idea","name":"Develop drugs in children first when the target is a children's target","route":"/ideas/idea-bio2-paediatric-first-development/"},{"id":"idea-bio2-mechanism-defined-baskets","kind":"idea","name":"Group trials by broken mechanism, not by organ or single mutation","route":"/ideas/idea-bio2-mechanism-defined-baskets/"},{"id":"idea-tr1-pathology-triggered-referral","kind":"idea","name":"The pathology lab triggers a trial referral the day a rare cancer is diagnosed","route":"/ideas/idea-tr1-pathology-triggered-referral/"}],"drug":[{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"entrectinib","kind":"drug","name":"Entrectinib","route":"/drugs/entrectinib/"},{"id":"larotrectinib","kind":"drug","name":"Larotrectinib","route":"/drugs/larotrectinib/"},{"id":"taletrectinib","kind":"drug","name":"Taletrectinib","route":"/drugs/taletrectinib/"}],"institution":[{"id":"inselspital-bern","kind":"institution","name":"Inselspital, Bern University Hospital / University Cancer Center Inselspital","route":"/institutions/inselspital-bern/"},{"id":"colorado-cancer-center","kind":"institution","name":"University of Colorado Cancer Center","route":"/institutions/colorado-cancer-center/"}],"pathway":[{"id":"oncogene-activation-two-hit","kind":"pathway","name":"Drivers, passengers & the two-hit model","route":"/pathways/oncogene-activation-two-hit/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}]}}