Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (757 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Amplification, Gene.
Where it fits in the MeSH classification
- Broader topics
- Gene Expression Regulation; Mutation; Mutagenesis
- See also
- Gene Dosage
Research landscape
PubMed indexes 17,943 records tagged with the MeSH heading “Gene Amplification” (counts retrieved 2026-10-29). 1,219 of them (6.8%) were published from 2020 onward, and the busiest period so far is through 1999 with 8,102 records.
Reviews account for 1,431 records (8.0%) and meta-analyses for 37. Randomized controlled trials number 61 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 8,102 |
| 2000-2009 | 4,971 |
| 2010-2019 | 3,651 |
| 2020 onward | 1,219 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,431 | 8.0% |
| Meta-analyses | 37 | 0.2% |
| Randomized controlled trials | 61 | 0.3% |
Method: PubMed query "Gene Amplification"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in genetics and genomics
Genetic findings vary widely in strength. A variant linked to a condition in one study may not replicate in other ancestries, and most common variants have small effects that are meaningful only in aggregate. Studies of rare, high-impact variants can support strong causal claims about a gene, while association studies describe statistical links that need functional and independent replication. Check the sample size, the ancestry of participants, whether results were replicated, and whether a laboratory or clinical outcome was actually measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium | 2021 | Research article Design not recorded in structured metadata | 199 | cc by PMID 34166060 · DOI · PMC8425837 |
| Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis | 2018 | Research article Design not recorded in structured metadata | 191 | cc by PMID 29728604 · DOI · PMC5935683 |
| Origins and impact of extrachromosomal DNA | 2024 | Research article Design not recorded in structured metadata | 183 | cc by PMID 39506150 · DOI · PMC11540846 |
| EcDNA-borne structural variants drive oncogenic fusion transcript amplification | 2026 | Research article Design not recorded in structured metadata | 12 | cc by PMID 41506267 · DOI · PMC13402033 |
Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium [1]
Abstract reading summary — source excerpts
- Opening excerpt
- PurposeRhabdomyosarcoma is the most common soft tissue sarcoma of childhood.
- Closing excerpt
- ConclusionThis is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (250 words)
PurposeRhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome.Patients and methodsTumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed.ResultsDNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In FOXO1 fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. BCOR (15%), NF1 (15%), and TP53 (13%) mutations were found at a higher incidence than previously reported and TP53 mutations were associated with worse outcomes in both fusion-negative and FOXO1 fusion-positive cases. Interestingly, mutations in RAS isoforms predominated in infants MYOD1 was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database (ClinOmics), containing all genomic variants, and clinical annotation including survival data.ConclusionThis is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34166060 · DOI · PMC8425837
Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies.
- Closing excerpt
- These concepts may be applicable to many patients with metastatic cancer.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
The oligometastasis hypothesis suggests a spectrum of metastatic virulence where some metastases are limited in extent and curable with focal therapies. A subset of patients with metastatic colorectal cancer achieves prolonged survival after resection of liver metastases consistent with oligometastasis. Here we define three robust subtypes of de novo colorectal liver metastasis through integrative molecular analysis. Patients with metastases exhibiting MSI-independent immune activation experience the most favorable survival. Subtypes with adverse outcomes demonstrate VEGFA amplification in concert with (i) stromal, mesenchymal, and angiogenic signatures, or (ii) exclusive NOTCH1 and PIK3C2B mutations with E2F/MYC activation. Molecular subtypes complement clinical risk stratification to distinguish low-risk, intermediate-risk, and high-risk patients with 10-year overall survivals of 94%, 45%, and 19%, respectively. Our findings provide a framework for integrated classification and treatment of metastasis and support the biological basis of curable oligometastatic colorectal cancer. These concepts may be applicable to many patients with metastatic cancer.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29728604 · DOI · PMC5935683
Origins and impact of extrachromosomal DNA [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer1,2.
- Closing excerpt
- These results shed light on why ecDNA is a substantial clinical problem that can cooperatively drive tumour growth signals, alter transcriptional landscapes and suppress the immune system.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (229 words)
Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer1,2. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.1% of tumour samples contain ecDNA. We reveal a pattern highly indicative of tissue-context-based selection for ecDNAs, linking their genomic content to their tissue of origin. We show that not only is ecDNA a mechanism for amplification of driver oncogenes, but it also a mechanism that frequently amplifies immunomodulatory and inflammatory genes, such as those that modulate lymphocyte-mediated immunity and immune effector processes. Moreover, ecDNAs carrying immunomodulatory genes are associated with reduced tumour T cell infiltration. We identify ecDNAs bearing only enhancers, promoters and lncRNA elements, suggesting the combinatorial power of interactions between ecDNAs in trans. We also identify intrinsic and environmental mutational processes linked to ecDNA, including those linked to its formation, such as tobacco exposure, and progression, such as homologous recombination repair deficiency. Clinically, ecDNA detection was associated with tumour stage, more prevalent after targeted therapy and cytotoxic treatments, and associated with metastases and shorter overall survival. These results shed light on why ecDNA is a substantial clinical problem that can cooperatively drive tumour growth signals, alter transcriptional landscapes and suppress the immune system.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39506150 · DOI · PMC11540846
EcDNA-borne structural variants drive oncogenic fusion transcript amplification [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Extrachromosomal DNA (ecDNA) amplifications are key drivers of human cancers.
- Closing excerpt
- These results demonstrate that ecDNA fosters genome instability and frequent oncogene fusion formation in cancer.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (128 words)
Extrachromosomal DNA (ecDNA) amplifications are key drivers of human cancers. Here, we show that ecDNAs are major platforms for generating and amplifying oncogene fusion transcripts across diverse cancer types. By integrating analysis of whole-genome and transcriptome sequences from tumor samples and cancer cell lines of a wide variety of tissue types, we reveal that ecDNAs have the highest rate of oncogene fusion events of any copy-number alteration. Focusing on the most common ecDNA fusion hotspot, we find that fusion of the 5' end of the long noncoding RNA gene, PVT1-with exon 1 joined to diverse 3' partners-confers increased RNA stability, potentially via an SRSF1-dependent mechanism, and enhances MYC-dependent transcription and cancer cell survival. These results demonstrate that ecDNA fosters genome instability and frequent oncogene fusion formation in cancer.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41506267 · DOI · PMC13402033
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Gene amplification [5]
- Research article Gene amplification in cultured animal cells [6]
- Research article Gene amplification in cancer [7]
- Research article DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies [8]
- Research article Recent progress in understanding mechanisms of mammalian DNA amplification [9]
- Research article Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond [10]
References
- Shern JF, Selfe J, Izquierdo E, Patidar R, Chou HC, Song YK, et al.. Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium. . 2021. PMID 34166060 · DOI · PMC8425837
- Pitroda SP, Khodarev NN, Huang L, Uppal A, Wightman SC, Ganai S, et al.. Integrated molecular subtyping defines a curable oligometastatic state in colorectal liver metastasis. . 2018. PMID 29728604 · DOI · PMC5935683
- Bailey C, Pich O, Thol K, Watkins TBK, Luebeck J, Rowan A, et al.. Origins and impact of extrachromosomal DNA. . 2024. PMID 39506150 · DOI · PMC11540846
- Yi H, Zhang S, Swinderman J, Wang Y, Kanakaveti V, Hung KL, et al.. EcDNA-borne structural variants drive oncogenic fusion transcript amplification. . 2026. PMID 41506267 · DOI · PMC13402033
- Stark GR, Wahl GM. Gene amplification. Annu Rev Biochem. 1984. PMID 6383198 · DOI
- Schimke RT. Gene amplification in cultured animal cells. Cell. 1984. PMID 6378386 · DOI
- Albertson DG. Gene amplification in cancer. Trends Genet. 2006. PMID 16787682 · DOI
- Knuutila S, Björkqvist AM, Autio K, Tarkkanen M, Wolf M, Monni O, et al.. DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol. 1998. PMID 9588877 · PMC1858578
- Stark GR, Debatisse M, Giulotto E, Wahl GM. Recent progress in understanding mechanisms of mammalian DNA amplification. Cell. 1989. PMID 2661014 · DOI
- Marchiò C, Annaratone L, Marques A, Casorzo L, Berrino E, Sapino A. Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond. Semin Cancer Biol. 2021. PMID 32112814 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.