{"entity":{"id":"gene-amplification","kind":"term","name":"Gene amplification and copy-number change","aka":["amplification","amplified","amplifications","copy number","copy-number","copy number alteration","copy number gain","gene copy number","MYCN-amplified","MET amplification","CCNE1 amplification","deletion","homozygous deletion","del(17p)","1q gain","loss of heterozygosity","LOH","genomic instability","chromosomal instability","aneuploidy"],"tldr":"Cancer cells often have extra copies of a growth gene (amplification) or have lost copies of a protective one (deletion), rather than a spelling change within the gene. Extra copies of HER2 or MYCN are classic examples that change treatment.","summary":"Amplification (detected by FISH, ISH or NGS copy-number calls) drives overexpression: HER2 in breast and gastric cancer, MYCN in high-risk neuroblastoma, MET amplification as a resistance route to EGFR inhibitors, CCNE1 in ovarian and gastric cancer, MDM2 in liposarcoma, CDK4 in glioma. Deletions remove tumour suppressors: del(17p)/TP53 in CLL and myeloma (predicting chemo-resistance), CDKN2A/B in glioma (defining grade 4), MTAP (creating a PRMT5 vulnerability), 9p21 loss linked to immunotherapy resistance. Loss of heterozygosity and large-scale copy changes are summed into genomic-scar scores used to infer HRD and predict PARP inhibitor benefit.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gene_duplication","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gene_duplication"}],"tags":[],"related":["fish","her2-positive","hrd","cytogenetics"],"cancers":[],"sections":["diagnostics"],"technologies":["cgp","histopathology-ihc"],"targets":["her2","mdm2","prmt5-mtap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/gene-amplification/","neighbours":{"term":[{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","route":"/terms/cytogenetics/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"her2-testing-in-biliary-cancer","kind":"term","name":"HER2 testing in biliary tract cancer (IHC, ISH and NGS)","route":"/terms/her2-testing-in-biliary-cancer/"},{"id":"her2-positive","kind":"term","name":"HER2-positive (IHC 3+ or ISH-amplified)","route":"/terms/her2-positive/"},{"id":"hrd","kind":"term","name":"Homologous recombination deficiency (HRD)","route":"/terms/hrd/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"fgfr1","kind":"target","name":"FGFR1","route":"/targets/fgfr1/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"mdm2","kind":"target","name":"MDM2","route":"/targets/mdm2/"},{"id":"mycn","kind":"target","name":"MYCN (N-myc)","route":"/targets/mycn/"},{"id":"prmt5-mtap","kind":"target","name":"PRMT5 (MTAP-deleted cancers)","route":"/targets/prmt5-mtap/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"},{"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":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"paper":[{"id":"paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011","kind":"paper","name":"A molecularly annotated platform of patient-derived xenografts identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","route":"/key-papers/paper-bertotti-xenopatients-her2-cetuximab-resistant-colorectal-cancer-discov-2011/"},{"id":"paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015","kind":"paper","name":"Assessment of a HER2 scoring system for colorectal cancer: results from a validation study","route":"/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/"},{"id":"paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021","kind":"paper","name":"Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)","route":"/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/"},{"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-weiss-fgfr1-amplification-squamous-lung-sci-transl-med-2010","kind":"paper","name":"Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer","route":"/key-papers/paper-weiss-fgfr1-amplification-squamous-lung-sci-transl-med-2010/"},{"id":"paper-quigley-structural-variation-mcrpc-cell-2018","kind":"paper","name":"Genomic hallmarks and structural variation in metastatic prostate cancer","route":"/key-papers/paper-quigley-structural-variation-mcrpc-cell-2018/"},{"id":"paper-visakorpi-androgen-receptor-amplification-nat-genet-1995","kind":"paper","name":"In vivo amplification of the androgen receptor gene and progression of human prostate cancer","route":"/key-papers/paper-visakorpi-androgen-receptor-amplification-nat-genet-1995/"},{"id":"paper-engelman-met-amplification-gefitinib-resistance-science-2007","kind":"paper","name":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","route":"/key-papers/paper-engelman-met-amplification-gefitinib-resistance-science-2007/"},{"id":"paper-awad-met-exon-14-mutations-lung-jco-2016","kind":"paper","name":"MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression","route":"/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/"},{"id":"paper-beltran-nepc-aurka-mycn-cancer-discov-2011","kind":"paper","name":"Molecular characterisation of neuroendocrine prostate cancer and identification of new drug targets","route":"/key-papers/paper-beltran-nepc-aurka-mycn-cancer-discov-2011/"},{"id":"paper-destiny-crc02-lancet-oncol-2024","kind":"paper","name":"Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial","route":"/key-papers/paper-destiny-crc02-lancet-oncol-2024/"},{"id":"paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023","kind":"paper","name":"Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)","route":"/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/"}],"biomarker":[{"id":"pd-ligand-9p24-alteration","kind":"biomarker","name":"9p24.1 alteration of the PD-1 ligand loci","route":"/biomarkers/pd-ligand-9p24-alteration/"},{"id":"ar-amplification","kind":"biomarker","name":"AR amplification (gene and upstream enhancer)","route":"/biomarkers/ar-amplification/"},{"id":"her2-ish-amplified","kind":"biomarker","name":"HER2 ISH amplified (ERBB2 gene amplification)","route":"/biomarkers/her2-ish-amplified/"},{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","route":"/biomarkers/met-amplification-readout/"},{"id":"mycn-amp","kind":"biomarker","name":"MYCN amplification","route":"/biomarkers/mycn-amp/"},{"id":"nectin-4-expression","kind":"biomarker","name":"Nectin-4 expression","route":"/biomarkers/nectin-4-expression/"}]}}