# MYC

Source: https://onco.cc/targets/myc-gene/  
OnCo record `myc-gene` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

MYC (Myc proto-oncogene protein) is a protein that switches other genes on and off. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Skin cancer, Multiple myeloma and 5 more.

## Summary

Transcription factor that binds DNA in a non-specific manner, yet also specifically recognises the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis.

CIViC holds 12 clinical evidence items and 0 assertions across 4 variants, naming Capmatinib, Olaparib, Pazopanib and Ganetespib and others. Open Targets scores its association with cancer at 0.74 (direct and indirect evidence; datatypes affected pathway 0.83, literature 1.00, genetic association 0.65, somatic mutation 0.81, animal model 0.52). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Acute Myeloid Leukaemia, Burkitt Lymphoma, Malignant Lymphoma, Non-Hodgkin Lymphoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: MYC proto-oncogene, bHLH transcription factor; Myc proto-oncogene protein; c-Myc; bHLHe39
- Tags: cancer-genes-wave
- Symbol: MYC
- Class: transcription
- Biology: Transcription factor that binds DNA in a non-specific manner, yet also specifically recognises the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release. Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. Location: Nucleus, nucleoplasm; Nucleus, nucleolus; Nucleus; Cytoplasm (UniProt). Locus 8q24.21 (HGNC).
- Where found: Non-Hodgkin lymphoma: Open Targets association 0.77 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM, NHL); Skin cancer: Open Targets association 0.60 with skin cancer (MONDO_0002898); Multiple myeloma: CIViC evidence names this disease; Oesophageal cancer: CIViC evidence names this disease; Bladder & urothelial cancer: Open Targets association 0.59 with urinary bladder cancer (MONDO_0001187); Leukaemia: Open Targets association 0.56 with leukaemia (MONDO_0005059); Pancreatic ductal adenocarcinoma: amplification 4-13%; Colorectal cancer: high-level amplification (8q24) 4-5%

## Notes

- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 9 therapies; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 12 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: High-grade B-cell Lymphoma, With MYC And BCL2 Rearrangements.
- Pancreatic ductal adenocarcinoma: amplified in 4 to 13% depending on platform (12.6% of 183 TCGA and 11.9% of 109 UTSW samples by array or exome, 4.2% on the MSK panel; cBioPortal). MYC amplification was uniquely associated with poor outcome and adenosquamous histology among 109 microdissected cancers (Witkiewicz 2015), varies between cells within squamous-feature tumours (Hayashi 2020) and lies downstream of the super-enhancers released by KDM6A loss (Andricovich 2018).
- Colorectal cancer: high-level amplification in 4 to 5% (cBioPortal), but the TCGA integrative reading is that MYC-directed transcriptional activation and repression is the common output of APC loss whether or not the gene is amplified, which is why MYC matters in a disease where it is rarely amplified (Cancer Genome Atlas Network 2012).
- Lung cancer: high-level amplification in about 7 to 8% of non-small-cell tumours (cBioPortal). In small-cell disease the three MYC paralogues are amplified in a mutually exclusive pattern and track the transcriptional state, MYCL with the ASCL1 subtype and MYC with the NEUROD1 subtype and the shift towards a less neuroendocrine phenotype (Rudin 2019).
- Lymphoma, MYC, and the double-hit and triple-hit definitions: MYC was mapped to 8q24, the region translocated to chromosome 2, 14 or 22 in Burkitt lymphoma cells, in 1982 (Dalla-Favera 1982); the partner is always an immunoglobulin locus, so the transcription factor is driven by the enhancer that should be driving antibody production. A double hit is a MYC rearrangement together with a BCL2 rearrangement, a triple hit adds BCL6. The two lesions are complementary rather than additive: MYC drives proliferation and would normally trigger apoptosis, and BCL2 removes that safeguard. Frequency: MYC rearrangement in 8.8% of 442 diffuse large B-cell lymphomas, BCL2 in 13.5% and BCL6 in 28.7% (Horn 2013). Protein overexpression is much commoner than rearrangement: MYC protein above the 40% threshold in 31.8% of the same cohort (Horn 2013), and in a separate 167-patient training cohort MYC protein in 29%, BCL2 protein in 44% and both together in 21%, against MYC translocation in only 11% (Johnson 2012). What it changes about treatment: The WHO fifth edition separates high-grade B-cell lymphoma with MYC and BCL2 rearrangements as its own entity (Alaggio 2022), and in practice a double hit moves most patients off R-CHOP onto a more intensive regimen, although the randomised evidence for doing so is thin. Double expression of the two proteins without rearrangement is prognostic, not a separate entity, and does not by itself change the regimen: in the trial cohort MYC protein predicted worse survival only when BCL2 protein was present too (Johnson 2012).
- Lymphoma, TP53 loss, in mantle cell lymphoma and in Richter transformation: TP53 is the commonest route by which a lymphoma stops responding to chemotherapy, because chemotherapy kills largely by provoking a p53-dependent death. In mantle cell lymphoma it travels with blastoid morphology, a high Ki-67 and CDKN2A deletion. In Richter transformation it is one of two lesions that dominate the genetics, and the transformed clone is usually the same clone as the leukaemia rather than a second cancer. Frequency: In 183 younger mantle cell lymphoma patients from the Nordic MCL2 and MCL3 trials, TP53 mutation in 11% and TP53 deletion in 16%, with CDKN2A deletion in 20% and NOTCH1 mutation in 4%; only TP53 mutation kept its prognostic weight in multivariable analysis, with a hazard ratio of 6.2 for overall survival, a median overall survival of 1.8 years against 12.7 years for unmutated cases, and half the mutated group relapsing within a year (Eskelund 2017). In 86 cases of Richter syndrome, TP53 disruption in 47.1% and MYC abnormality in 26.2%; clonally unrelated transformations had both a longer median survival, 62.5 against 14.2 months, and less TP53 disruption, 23.1% against 60.0% (Rossi 2011). What it changes about treatment: In mantle cell lymphoma, yes in practice if not yet on any label: a TP53 mutation is the usual reason to abandon intensive cytarabine-based induction and autologous transplant and to go to a BTK inhibitor, a BCL-2 inhibitor or CAR-T instead. In Richter transformation it is the main prognostic variable, and establishing whether the large-cell clone is related to the leukaemic one changes the expected outcome more than any drug does.
- Lymphoma, Epstein-Barr virus and its latency programmes: Epstein-Barr virus persists for life in the memory B-cell pool of almost everyone, and what it expresses while it is there decides what it can cause. In latency I only EBNA1 is made, which is enough to keep the episome but gives the immune system almost nothing to see; this is the Burkitt pattern, where the virus coexists with a MYC translocation. In latency II, EBNA1 with LMP1 and LMP2, LMP1 mimics a permanently engaged CD40 receptor and drives NF-kB; this is the Hodgkin and NK/T-cell pattern. In latency III the full set of nuclear antigens and membrane proteins is expressed and will immortalise a resting B cell outright, which is what happens when T-cell surveillance is removed, as in post-transplant lymphoproliferative disorder and HIV-associated lymphoma. The virus was found in the first place by electron microscopy of cells cultured from Burkitt lymphoma, whose geographic distribution matching holoendemic malaria had suggested a viral cause (Young and Rickinson 2004). Frequency: The share of each disease that is EBV-positive varies by subtype, by geography and by age, and this layer does not state a single figure because the published ranges are wide and cohort-dependent. What is consistent is the direction: the proportion rises with immunosuppression and with age, and endemic Burkitt lymphoma in equatorial Africa is almost uniformly positive while sporadic Burkitt lymphoma usually is not. What it changes about treatment: Reducing immunosuppression is the first treatment of post-transplant lymphoproliferative disorder, which is the only place where acting on the virus changes the plan. Plasma EBV DNA is used to monitor response in NK/T-cell lymphoma and in post-transplant disease. EBV-specific T cells are licensed for post-transplant disease after transplant failure.
- Lymphoma, TCF3, ID3 and CCND3 in Burkitt lymphoma: A MYC translocation alone does not make a Burkitt lymphoma; it needs a partner that supplies survival. In Burkitt the partner is tonic B-cell receptor signalling through TCF3, the transcription factor also known as E2A: mutations either activate TCF3 or inactivate its negative regulator ID3, and TCF3 then switches on the PI3K pathway partly by augmenting tonic receptor signalling. A second, independent lesion drives the cell cycle directly, through CCND3 mutations that produce unusually stable cyclin D3. Frequency: TCF3 or ID3 mutation in 70% of sporadic Burkitt lymphoma cases and oncogenic CCND3 mutations in 38%, in a study combining high-throughput RNA sequencing with RNA interference screening (Schmitz 2012). What it changes about treatment: Not yet, and the gap is uncomfortable, because the regimens that cure Burkitt lymphoma are the most toxic in lymphoma and are the reason the disease is hard to treat in older patients and in low-resource settings, which is exactly where the endemic form occurs.

## Sources

- HGNC HGNC:7553: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7553
- UniProt P01106: https://www.uniprot.org/uniprotkb/P01106/entry
- NCBI Gene 4609: https://www.ncbi.nlm.nih.gov/gene/4609
- Ensembl ENSG00000136997: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000136997
- Dalla-Favera et al., PNAS 1982: human c-myc lies in the chromosome 8 region translocated in Burkitt lymphoma: https://doi.org/10.1073/pnas.79.24.7824
- Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients: https://doi.org/10.1182/blood-2012-06-435842
- Johnson et al., J Clin Oncol 2012: concurrent MYC and BCL2 protein expression in diffuse large B-cell lymphoma treated with R-CHOP: https://doi.org/10.1200/JCO.2011.41.0985
- Alaggio et al., Leukemia 2022: the fifth edition of the WHO classification of haematolymphoid tumours, lymphoid neoplasms: https://doi.org/10.1038/s41375-022-01620-2
- Eskelund et al., Blood 2017: TP53 mutations in 183 younger mantle cell lymphoma patients from Nordic MCL2 and MCL3: https://doi.org/10.1182/blood-2017-04-779736
- Rossi et al., Blood 2011: the genetics of Richter syndrome in 86 pathologically proven cases: https://doi.org/10.1182/blood-2010-09-302174
- Young and Rickinson, Nat Rev Cancer 2004: Epstein-Barr virus, 40 years on: https://doi.org/10.1038/nrc1452
- Kuppers, Nat Rev Cancer 2009: the biology of Hodgkin's lymphoma: https://doi.org/10.1038/nrc2542
- Schmitz et al., Nature 2012: Burkitt lymphoma pathogenesis from structural and functional genomics: https://doi.org/10.1038/nature11378

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Leukaemia (all types)](https://onco.cc/cancers/leukaemia/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Skin cancer (all types)](https://onco.cc/cancers/skin-cancer/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- pathways: [B-cell receptor / BTK signalling (to NF-κB)](https://onco.cc/pathways/bcr-signalling/), [Basal cell carcinoma (KEGG map)](https://onco.cc/pathways/basal-cell-carcinoma-signalling/), [Bladder cancer (KEGG map)](https://onco.cc/pathways/bladder-cancer-signalling/), [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Chromosomal instability & aneuploidy](https://onco.cc/pathways/chromosomal-instability/), [Circadian control](https://onco.cc/pathways/circadian-control/), [DNA replication & origin licensing](https://onco.cc/pathways/dna-replication-licensing/), [DNA replication stress](https://onco.cc/pathways/replication-stress/), [Glutamine addiction](https://onco.cc/pathways/glutamine-metabolism/), [Inflammation & NF-κB](https://onco.cc/pathways/inflammation-nfkb/), [MicroRNAs in cancer](https://onco.cc/pathways/micrornas-in-cancer/), [mRNA translation (eIF4F / mTOR)](https://onco.cc/pathways/mrna-translation-eif4f/), [MYC](https://onco.cc/pathways/myc/), [Notch signalling](https://onco.cc/pathways/notch/), [Oestrogen receptor signalling](https://onco.cc/pathways/er-signaling/), [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Small cell lung cancer (KEGG map)](https://onco.cc/pathways/sclc-signalling/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/), [The germinal centre reaction](https://onco.cc/pathways/germinal-centre-reaction/), [The p53 network (guardian of the genome)](https://onco.cc/pathways/p53-mdm2-axis/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- key papers: [A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma](https://onco.cc/key-papers/paper-hayashi-squamous-basal-like-pancreatic-nat-cancer-2020/), [Comprehensive genomic profiles of small cell lung cancer](https://onco.cc/key-papers/paper-george-sclc-genomic-profiles-nature-2015/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Loss of KDM6A activates super-enhancers to induce gender-specific squamous-like pancreatic cancer and confers sensitivity to BET inhibitors](https://onco.cc/key-papers/paper-andricovich-kdm6a-squamous-pancreatic-cancer-cell-2018/), [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/), [Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets](https://onco.cc/key-papers/paper-witkiewicz-pancreatic-exomes-utsw-nat-commun-2015/)
- terms: [Double-hit / high-grade B-cell lymphoma](https://onco.cc/terms/double-hit-lymphoma/), [Epstein-Barr virus latency programmes, and why they decide which lymphoma](https://onco.cc/terms/lymphoma-bio-ebv-latency/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/), [Transformation: when a slow lymphoma turns into a fast one](https://onco.cc/terms/lymphoma-bio-transformation/)
- biomarkers: [Double expressor: MYC and BCL2 protein together by immunohistochemistry](https://onco.cc/biomarkers/myc-bcl2-double-expressor/), [Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement](https://onco.cc/biomarkers/double-hit-rearrangement/)

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