# Driver mutation

Source: https://onco.cc/terms/driver-mutation/  
OnCo record `driver-mutation` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations
- Wikipedia: https://en.wikipedia.org/wiki/Carcinogenesis#Driver_and_passenger_mutations

## Connected records

- terms: [Actionable genomic biomarkers](https://onco.cc/terms/cancer-drivers-vs-actionable/), [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Driver and passenger mutations: the refined somatic mutation theory](https://onco.cc/terms/driver-passenger-model/), [EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)](https://onco.cc/terms/egfr-mutation-subtypes/), [Gene fusion](https://onco.cc/terms/gene-fusion/), [Genomic profiling](https://onco.cc/terms/genomic-profiling/), [KRAS mutation subtypes (G12C, G12D, G12V)](https://onco.cc/terms/kras-mutation-subtypes/), [Lung cancer trials open today (registry snapshot)](https://onco.cc/terms/lung-trials-open-today/), [Mutation](https://onco.cc/terms/mutation/), [MutSig (significantly mutated gene detection)](https://onco.cc/terms/mutsig/), [Oncogene](https://onco.cc/terms/oncogene/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/), [Somatic mutation theory of cancer](https://onco.cc/terms/somatic-mutation-theory/), [Targeted therapy](https://onco.cc/terms/targeted-therapy-term/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/), [Tumour suppressor gene](https://onco.cc/terms/tumour-suppressor-gene/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/), [Wild-type (WT)](https://onco.cc/terms/wild-type/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Companion diagnostics](https://onco.cc/technologies/companion-diagnostic/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/), [APC](https://onco.cc/targets/apc/), [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/), [KRAS](https://onco.cc/targets/kras/), [TP53](https://onco.cc/targets/tp53/)
- cancers: [Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)](https://onco.cc/cancers/advanced-systemic-mastocytosis/), [BRAF V600E-mutant non-small-cell lung cancer](https://onco.cc/cancers/braf-v600e-nsclc/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Erdheim-Chester disease](https://onco.cc/cancers/erdheim-chester-disease/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [HER2-mutant non-small-cell lung cancer](https://onco.cc/cancers/her2-mutant-nsclc/), [Indolent and smouldering systemic mastocytosis](https://onco.cc/cancers/indolent-systemic-mastocytosis/), [KRAS G12C-mutant non-small-cell lung cancer](https://onco.cc/cancers/kras-g12c-nsclc/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [MET exon 14 and MET-amplified non-small-cell lung cancer](https://onco.cc/cancers/met-altered-nsclc/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Rosai-Dorfman-Destombes disease](https://onco.cc/cancers/rosai-dorfman-disease/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Systemic mastocytosis](https://onco.cc/cancers/systemic-mastocytosis/)
- key papers: [A genetic model for colorectal tumorigenesis](https://onco.cc/key-papers/paper-fearon-cell/), [Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-lynch-egfr-activating-mutations-gefitinib-nejm-2004/), [Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer](https://onco.cc/key-papers/paper-peters-alex-alectinib-crizotinib-nejm-2017/), [Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer](https://onco.cc/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/), [Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer](https://onco.cc/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/), [CD74-NRG1 fusions in lung adenocarcinoma](https://onco.cc/key-papers/paper-fernandez-cuesta-cd74-nrg1-fusion-lung-cancer-discov-2014/), [CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug](https://onco.cc/key-papers/paper-codebreak-200-lancet-2023/), [Comprehensive genomic characterization of squamous cell lung cancers](https://onco.cc/key-papers/paper-tcga-lung-squamous-nature-2012/), [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Comprehensive molecular profiling of lung adenocarcinoma](https://onco.cc/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/), [Core signaling pathways in human pancreatic cancers revealed by global genomic analyses](https://onco.cc/key-papers/paper-jones-pancreatic-core-pathways-science-2008/), [Differences in prostate cancer genomes by self-reported race](https://onco.cc/key-papers/paper-stopsack-prostate-genomes-by-race-ccr-2022/), [Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas](https://onco.cc/key-papers/paper-campbell-pan-lung-somatic-alterations-nat-genet-2016/), [EGFR mutation and resistance of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/), [EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy](https://onco.cc/key-papers/paper-paez-egfr-mutations-gefitinib-science-2004/), [Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer](https://onco.cc/key-papers/paper-barbieri-spop-foxa1-med12-prostate-nat-genet-2012/), [Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma](https://onco.cc/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/), [Genetic alterations during colorectal-tumor development](https://onco.cc/key-papers/paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988/), [Genomic and evolutionary classification of lung cancer in never smokers](https://onco.cc/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/), [Genomic correlates of clinical outcome in advanced prostate cancer](https://onco.cc/key-papers/paper-abida-genomic-correlates-outcome-mcrpc-pnas-2019/), [Genomic landscape of lung adenocarcinoma in East Asians](https://onco.cc/key-papers/paper-chen-east-asian-lung-adenocarcinoma-nat-genet-2020/), [Genomics of lethal prostate cancer at diagnosis and castration resistance](https://onco.cc/key-papers/paper-mateo-genomics-lethal-prostate-diagnosis-castration-resistance-jci-2020/), [Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer](https://onco.cc/key-papers/paper-soda-eml4-alk-fusion-nature-2007/), [K-ras mutations and benefit from cetuximab in advanced colorectal cancer](https://onco.cc/key-papers/paper-karapetis-kras-cetuximab-colorectal-nejm-2008/), [Lung adenocarcinoma promotion by air pollutants](https://onco.cc/key-papers/paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023/), [MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-mariposa-nejm-2024/), [Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data](https://onco.cc/key-papers/paper-rudin-sclc-molecular-subtypes-nat-rev-cancer-2019/), [Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer](https://onco.cc/key-papers/paper-taplin-ar-mutation-androgen-independent-prostate-nejm-1995/), [Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer](https://onco.cc/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/), [Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC](https://onco.cc/key-papers/paper-lu-laura-osimertinib-stage-iii-nejm-2024/), [Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC](https://onco.cc/key-papers/paper-planchard-flaura2-osimertinib-chemotherapy-nejm-2023/), [Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies](https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/), [Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer](https://onco.cc/key-papers/paper-tomlins-tmprss2-ets-fusion-science-2005/), [ROS1 rearrangements define a unique molecular class of lung cancers](https://onco.cc/key-papers/paper-bergethon-ros1-rearrangements-lung-jco-2012/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [TCGA: the molecular taxonomy of primary prostate cancer](https://onco.cc/key-papers/paper-tcga-molecular-taxonomy-primary-prostate-cell-2015/), [The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer](https://onco.cc/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/), [The landscape of somatic mutation in normal colorectal epithelial cells](https://onco.cc/key-papers/paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019/), [The long tail of oncogenic drivers in prostate cancer](https://onco.cc/key-papers/paper-armenia-long-tail-oncogenic-drivers-prostate-nat-genet-2018/), [The mutational landscape of lethal castration-resistant prostate cancer](https://onco.cc/key-papers/paper-grasso-mutational-landscape-lethal-crpc-nature-2012/), [TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse](https://onco.cc/key-papers/paper-tracerx-100-nejm-2017/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/), [Whole-genome and transcriptome sequencing of prostate cancer identifies new genetic alterations driving disease progression](https://onco.cc/key-papers/paper-ren-chinese-prostate-whole-genome-eur-urol-2018/)
- trials: [BRF113928 cohort C (dabrafenib with trametinib, untreated BRAF V600E)](https://onco.cc/trials/brf113928/)
- biomarkers: [AR ligand-binding-domain mutation (L702H, W742C, H875Y, T878A, F877L)](https://onco.cc/biomarkers/ar-ligand-binding-domain-mutation/), [RHOA G17V](https://onco.cc/biomarkers/rhoa-g17v/), [SPOP mutation](https://onco.cc/biomarkers/spop-mutation/), [TMPRSS2-ERG fusion (and the other ETS rearrangements)](https://onco.cc/biomarkers/tmprss2-erg-fusion/)
- pathways: [Theories of cancer: how the ideas connect](https://onco.cc/pathways/theories-of-cancer/)

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