{"entity":{"id":"driver-mutation","kind":"term","name":"Driver mutation","aka":["driver mutations","driver","drivers","oncogenic driver","oncogenic drivers","driver alteration","driver alterations","driver gene","driver genes","passenger mutation","passenger mutations","driver mutation","oncogene-driven","driver-positive","driver-negative","actionable","actionable mutation","actionable alteration","targetable","targetable driver","targetable mutation","molecularly selected","biomarker-driven","actionable alterations","targetable drivers","targetable mutations","driver-mutation-term"],"tldr":"One of the few mutations in a tumour that actually causes it to grow. Everything else is a passenger along for the ride. Drivers are the mutations drugs are aimed at.","summary":"A tumour with thousands of mutations usually has two to eight drivers that confer a growth advantage; the rest are passengers that happened to be present in the cell that became cancerous. Drivers cluster in a few hundred genes: oncogenes activated by mutation or amplification (EGFR, KRAS, BRAF, HER2, ALK) and tumour suppressors lost by mutation or deletion (TP53, RB1, PTEN). Genomic profiling looks for known drivers because a tumour that depends on one can often be treated with a drug against it, the phenomenon called oncogene addiction.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations"}],"tags":[],"related":["mutation","oncogene","tumour-suppressor-gene","oncogene-addiction","genomic-profiling","targeted-therapy-term","egfr-mutation-subtypes","kras-mutation-subtypes","braf-v600-mutation","gene-fusion","tumour-agnostic","driver-passenger-model","somatic-mutation-theory"],"cancers":[],"sections":["targeted-therapy","diagnostics"],"technologies":["cgp","kinase-inhibitors","companion-diagnostic"],"targets":["egfr","kras","braf","alk","tp53"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},"route":"/terms/driver-mutation/","neighbours":{"term":[{"id":"cancer-drivers-vs-actionable","kind":"term","name":"Actionable genomic biomarkers","route":"/terms/cancer-drivers-vs-actionable/"},{"id":"braf-v600-mutation","kind":"term","name":"BRAF V600E mutation","route":"/terms/braf-v600-mutation/"},{"id":"driver-passenger-model","kind":"term","name":"Driver and passenger mutations: the refined somatic mutation theory","route":"/terms/driver-passenger-model/"},{"id":"egfr-mutation-subtypes","kind":"term","name":"EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)","route":"/terms/egfr-mutation-subtypes/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"genomic-profiling","kind":"term","name":"Genomic profiling","route":"/terms/genomic-profiling/"},{"id":"kras-mutation-subtypes","kind":"term","name":"KRAS mutation subtypes (G12C, G12D, G12V)","route":"/terms/kras-mutation-subtypes/"},{"id":"lung-trials-open-today","kind":"term","name":"Lung cancer trials open today (registry snapshot)","route":"/terms/lung-trials-open-today/"},{"id":"mutation","kind":"term","name":"Mutation","route":"/terms/mutation/"},{"id":"mutsig","kind":"term","name":"MutSig (significantly mutated gene detection)","route":"/terms/mutsig/"},{"id":"oncogene","kind":"term","name":"Oncogene","route":"/terms/oncogene/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"},{"id":"somatic-mutation-theory","kind":"term","name":"Somatic mutation theory of cancer","route":"/terms/somatic-mutation-theory/"},{"id":"targeted-therapy-term","kind":"term","name":"Targeted therapy","route":"/terms/targeted-therapy-term/"},{"id":"lymphoma-bio-germinal-centre","kind":"term","name":"The germinal centre: why lymphoma starts where antibodies are made","route":"/terms/lymphoma-bio-germinal-centre/"},{"id":"tumour-suppressor-gene","kind":"term","name":"Tumour suppressor gene","route":"/terms/tumour-suppressor-gene/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"},{"id":"wild-type","kind":"term","name":"Wild-type (WT)","route":"/terms/wild-type/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"companion-diagnostic","kind":"technology","name":"Companion diagnostics","route":"/technologies/companion-diagnostic/"},{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"apc","kind":"target","name":"APC","route":"/targets/apc/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"cancer":[{"id":"advanced-systemic-mastocytosis","kind":"cancer","name":"Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)","route":"/cancers/advanced-systemic-mastocytosis/"},{"id":"braf-v600e-nsclc","kind":"cancer","name":"BRAF V600E-mutant non-small-cell lung cancer","route":"/cancers/braf-v600e-nsclc/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"erdheim-chester-disease","kind":"cancer","name":"Erdheim-Chester disease","route":"/cancers/erdheim-chester-disease/"},{"id":"histiocytoses","kind":"cancer","name":"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms","route":"/cancers/histiocytoses/"},{"id":"her2-mutant-nsclc","kind":"cancer","name":"HER2-mutant non-small-cell lung cancer","route":"/cancers/her2-mutant-nsclc/"},{"id":"indolent-systemic-mastocytosis","kind":"cancer","name":"Indolent and smouldering systemic mastocytosis","route":"/cancers/indolent-systemic-mastocytosis/"},{"id":"kras-g12c-nsclc","kind":"cancer","name":"KRAS G12C-mutant non-small-cell lung cancer","route":"/cancers/kras-g12c-nsclc/"},{"id":"kras-g12c-pdac","kind":"cancer","name":"KRAS G12C-mutant pancreatic ductal adenocarcinoma","route":"/cancers/kras-g12c-pdac/"},{"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":"met-altered-nsclc","kind":"cancer","name":"MET exon 14 and MET-amplified non-small-cell lung cancer","route":"/cancers/met-altered-nsclc/"},{"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":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rosai-dorfman-disease","kind":"cancer","name":"Rosai-Dorfman-Destombes disease","route":"/cancers/rosai-dorfman-disease/"},{"id":"sclc","kind":"cancer","name":"Small-cell lung cancer","route":"/cancers/sclc/"},{"id":"systemic-mastocytosis","kind":"cancer","name":"Systemic mastocytosis","route":"/cancers/systemic-mastocytosis/"}],"paper":[{"id":"paper-fearon-cell","kind":"paper","name":"A genetic model for colorectal tumorigenesis","route":"/key-papers/paper-fearon-cell/"},{"id":"paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004","kind":"paper","name":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/"},{"id":"paper-peters-alex-alectinib-crizotinib-nejm-2017","kind":"paper","name":"Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer","route":"/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/"},{"id":"paper-kwak-crizotinib-alk-nsclc-nejm-2010","kind":"paper","name":"Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer","route":"/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/"},{"id":"paper-wolf-geometry-mono-1-capmatinib-nejm-2020","kind":"paper","name":"Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer","route":"/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/"},{"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-codebreak-200-lancet-2023","kind":"paper","name":"CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug","route":"/key-papers/paper-codebreak-200-lancet-2023/"},{"id":"paper-tcga-lung-squamous-nature-2012","kind":"paper","name":"Comprehensive genomic characterization of squamous cell lung cancers","route":"/key-papers/paper-tcga-lung-squamous-nature-2012/"},{"id":"paper-george-sclc-genomic-profiles-nature-2015","kind":"paper","name":"Comprehensive genomic profiles of small cell lung cancer","route":"/key-papers/paper-george-sclc-genomic-profiles-nature-2015/"},{"id":"paper-tcga-lung-adenocarcinoma-nature-2014","kind":"paper","name":"Comprehensive molecular profiling of lung adenocarcinoma","route":"/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/"},{"id":"paper-jones-pancreatic-core-pathways-science-2008","kind":"paper","name":"Core signaling pathways in human pancreatic cancers revealed by global genomic analyses","route":"/key-papers/paper-jones-pancreatic-core-pathways-science-2008/"},{"id":"paper-stopsack-prostate-genomes-by-race-ccr-2022","kind":"paper","name":"Differences in prostate cancer genomes by self-reported race","route":"/key-papers/paper-stopsack-prostate-genomes-by-race-ccr-2022/"},{"id":"paper-campbell-pan-lung-somatic-alterations-nat-genet-2016","kind":"paper","name":"Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas","route":"/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/"},{"id":"paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005","kind":"paper","name":"EGFR mutation and resistance of non-small-cell lung cancer to gefitinib","route":"/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/"},{"id":"paper-paez-egfr-mutations-gefitinib-science-2004","kind":"paper","name":"EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy","route":"/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/"},{"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-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009","kind":"paper","name":"Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma","route":"/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/"},{"id":"paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988","kind":"paper","name":"Genetic alterations during colorectal-tumor development","route":"/key-papers/paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988/"},{"id":"paper-zhang-lung-cancer-never-smokers-nat-genet-2021","kind":"paper","name":"Genomic and evolutionary classification of lung cancer in never smokers","route":"/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/"},{"id":"paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019","kind":"paper","name":"Genomic correlates of clinical outcome in advanced prostate cancer","route":"/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/"},{"id":"paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020","kind":"paper","name":"Genomic landscape of lung adenocarcinoma in East Asians","route":"/key-papers/paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020/"},{"id":"paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020","kind":"paper","name":"Genomics of lethal prostate cancer at diagnosis and castration resistance","route":"/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/"},{"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-karapetis-kras-cetuximab-colorectal-nejm-2008","kind":"paper","name":"K-ras mutations and benefit from cetuximab in advanced colorectal cancer","route":"/key-papers/paper-karapetis-kras-cetuximab-colorectal-nejm-2008/"},{"id":"paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","kind":"paper","name":"Lung adenocarcinoma promotion by air pollutants","route":"/key-papers/paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023/"},{"id":"paper-mariposa-nejm-2024","kind":"paper","name":"MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer","route":"/key-papers/paper-mariposa-nejm-2024/"},{"id":"paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019","kind":"paper","name":"Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data","route":"/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/"},{"id":"paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995","kind":"paper","name":"Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer","route":"/key-papers/paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995/"},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","route":"/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/"},{"id":"paper-lu-laura-osimertinib-stage-iii-nejm-2024","kind":"paper","name":"Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC","route":"/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/"},{"id":"paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023","kind":"paper","name":"Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC","route":"/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/"},{"id":"paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017","kind":"paper","name":"Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies","route":"/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/"},{"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-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-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"},{"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-schoenfeld-smarca4-alterations-lung-ccr-2020","kind":"paper","name":"The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer","route":"/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/"},{"id":"paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019","kind":"paper","name":"The landscape of somatic mutation in normal colorectal epithelial cells","route":"/key-papers/paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019/"},{"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-tracerx-100-nejm-2017","kind":"paper","name":"TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse","route":"/key-papers/paper-tracerx-100-nejm-2017/"},{"id":"paper-kris-lung-cancer-mutation-consortium-jama-2014","kind":"paper","name":"Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs","route":"/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/"},{"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/"}],"trial":[{"id":"brf113928","kind":"trial","name":"BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)","route":"/trials/brf113928/"}],"biomarker":[{"id":"ar-ligand-binding-domain-mutation","kind":"biomarker","name":"AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)","route":"/biomarkers/ar-ligand-binding-domain-mutation/"},{"id":"rhoa-g17v","kind":"biomarker","name":"RHOA G17V","route":"/biomarkers/rhoa-g17v/"},{"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/"}],"pathway":[{"id":"theories-of-cancer","kind":"pathway","name":"Theories of cancer: how the ideas connect","route":"/pathways/theories-of-cancer/"}]}}