MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian))

2012-02-01   Tiangang Zhuang , Mayumi Higashi , Venkatadri Kolla , Garrett M Brodeur 

Childrens Hospital of Philadelphia, Oncology Research, CTRB Rm 3018, 3501 Civic Center Blvd, Philadelphia, PA 19104, USA


Atlas Image
MYCN (2p24). Fluorescence in-situ hybridization of MYCN probe to metaphase spread (Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics).
Atlas Image
MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)) Hybridization with Vysis LSI N-MYC (2p24) SpectrumG reen/Vysis CEP 2 SpectrumOrange probe (Abbott Molecular, US) showing the gene on 2p24 (green signals - Courtesy Adriana Zamecnikova.



3 exons.



MYCN is expressed in brain, eye, heart, kidney, lung, muscle, ovary, placenta and thymus. It is also expressed highly in several tumors: glioma, lung tumor, primitive neuroectodermal tumor, retinoblastoma (EST Profile).




Probable transcription factor; possible role during tissue differentiation.


With members of the myc family of helix-loop-helix transcription factors.



Amplification, either in extrachromosomal double minutes (DMs) or in homogeneously staining regions within chromosomes (there is amplification when, for example, 10 to 1000 copies of a gene are present in a cell); found amplified in a variety of human tumors, in particular in neuroblastoma and also in retinoblastoma, small cell lung carcinoma, astrocytoma; level of amplification related to the tumor progression; transgenic mice that overexpress MYCN in neuroectodermal cells develop neuroblastoma.

Implicated in

Entity name
Neuroblastoma karyotypes frequently reveal the cytogenetic hallmarks of gene amplification, namely DMs or HSRs. Schwab (Schwab et al., 1983) and Kohl (Kohl et al., 1983) originally identified the MYC-related oncogene MYCN as the target of this amplification event. MYCN is located on the distal short arm of chromosome 2 (2p24), but in cells with MYCN amplification, the extra copies reside within these DMs or HSRs (Schwab et al., 1984). Additional genes may be coamplified with MYCN in a subset of cases (DDX1, NAG, ALK), but MYCN is the only gene that is consistently amplified from this locus. The magnitude of MYCN amplification varies, but it averages 100-200 copies per cell (range 5-500+ copies).
The overall prevalence of MYCN amplification is 18-20%. Amplification of MYCN is associated with advanced stages of disease, unfavorable biological features, and a poor outcome (Brodeur et al., 1984; Seeger et al., 1985), but it is also associated with poor outcome in otherwise favorable patient groups (such as infants, and patients with lower stages of disease), underscoring its biological importance (Seeger et al., 1985; Look et al., 1991; Tonini et al., 1997; Katzenstein et al., 1998; Bagatell et al., 2005; George et al., 2005; Schneiderman et al., 2008). Therefore, the status of the MYCN gene is routinely determined from neuroblastoma samples obtained at diagnosis to assist in therapy planning (Look et al., 1991; Schwab et al., 2004). Indeed, because of the dramatic degree of MYCN amplification and consequent overexpression in a subset of aggressive neuroblastomas, it should be an attractive therapeutic target (Pession and Tonelli, 2005; Bell et al., 2010).
Weiss and colleagues (Weiss et al., 1997) created a transgenic mouse model of neuroblastoma, with MYCN expression driven in adrenergic cells by the tyrosine hydroxylase promoter (TH-MYCN mouse). Genomic changes in neuroblastomas arising in TH-MYCN mice closely parallel the genomic changes found characteristically in human tumors (Hackett et al., 2003). Thus, the TH-MYCN mouse model appears to be a tractable model to study neuroblastoma development, progression and therapy (Chessler and Weiss, 2011).
Atlas Image
Fluorescence in-situ hybridization of MYCN probe to metaphase and interphase nuclei of a primary neuroblastoma with MYCN amplification (Courtesy Garrett M. Brodeur, Childrens Hospital of Philadelphia).
Entity name
MYCN amplification is less common in medulloblastoma, a neural brain tumor of childhood, but it is also associated with a worse clinical outcome (Pfister et al., 2009). However, recent evidence suggests that MYCN overexpression is much more common in medulloblastomas, compared to normal cerebellum (Swartling et al., 2010), and it may drive the initiation or progression of medulloblastomas independent of the sonic hedgehog (SHH) pathway. Indeed, MYCN amplification is found in both SHH-driven and non-SHH-driven medulloblastomas, but each subtype is associated with other genetic features, suggesting they represent genetically distinct subtypes with different prognoses (Korshunov et al., 2011).
Entity name
Rhabdomyosarcoma (RMS)
MYCN amplification also occurs in a subset of RMS, the most common pediatric soft tissue sarcoma, although it tends to be at a lower level (4-20 fold) than is found in neuroblastomas. Amplification is found predominantly in the alveolar subsest of RMS, and it is rarely found in the more common form, called embryonal RMS (Driman et al., 1994). However, MYCN expression is found in the vast majority of RMS tumors, regardless of histology, at least in primary tumors (Toffolatti et al., 2002). For this reason, Morgenstern and Anderson have suggested that it would be an attractive therapeutic target for this disease (Morgenstern and Anderson, 2006).
Entity name
Wilms tumor
Wilms tumor may occasionally show amplification of the MYCN protooncogene (Schaub et al., 2007). MYCN amplification is consistently associated with overexpression, at least at the mRNA level. Initially, MYCN amplification was associated almost exclusively with the unfavorable, anaplastic subset of Wilms tumors. However, Williams and colleagues (Williams et al., 2011) found focal gain of MYCN in a substantial number of both anaplastic and favorable histologies in a survey of over 400 tumors, suggesting that other genomic changes may account for differences in clinical behavior.
Entity name
Other tumors (retinoblastoma, small cell lung cancer, glioblastoma multiforme)
About 3-5% of primary retinoblastomas have MYCN amplification, whereas it is much more common (27%) in established retinoblastoma cell lines (Bowles et al., 2007; Kim et al., 2008). MYCN is amplified in 15-25% of small cell lung cancers, and it may be more common in tumors at relapse (Johnson et al., 1987; Johnson et al., 1992). MYCN amplification rarely occurs in other lung cancer histologies (Yokota et al., 1988). MYCN amplification occurs in a substantial number of glioblastoma multiformes (Hui et al., 2001; Hodgson et al., 2008), but it is rarely found in lower grade gliomas and astrocytomas.


Pubmed IDLast YearTitleAuthors
163146422005Outcomes of children with intermediate-risk neuroblastoma after treatment stratified by MYCN status and tumor cell ploidy.Bagatell R et al
201539252010MYCN oncoprotein targets and their therapeutic potential.Bell E et al
170998722007Profiling genomic copy number changes in retinoblastoma beyond loss of RB1.Bowles E et al
67191371984Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.Brodeur GM et al
219589442011Genetically engineered murine models--contribution to our understanding of the genetics, molecular pathology and therapeutic targeting of neuroblastoma.Chesler L et al
81565311994MYCN gene amplification in rhabdomyosarcoma.Driman D et al
161161522005Hyperdiploidy plus nonamplified MYCN confers a favorable prognosis in children 12 to 18 months old with disseminated neuroblastoma: a Pediatric Oncology Group study.George RE et al
145003572003Genome-wide array CGH analysis of murine neuroblastoma reveals distinct genomic aberrations which parallel those in human tumors.Hackett CS et al
191394202009Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.Hodgson JG et al
113510432001Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization.Hui AB et al
13270351992myc family DNA amplification in tumors and tumor cell lines from patients with small-cell lung cancer.Johnson BE et al
96261971998Prognostic significance of age, MYCN oncogene amplification, tumor cell ploidy, and histology in 110 infants with stage D(S) neuroblastoma: the pediatric oncology group experience--a pediatric oncology group study.Katzenstein HM et al
185383702008N-myc amplification was rarely detected by fluorescence in situ hybridization in retinoblastoma.Kim JH et al
61971791983Transposition and amplification of oncogene-related sequences in human neuroblastomas.Kohl NE et al
221604022012Biological and clinical heterogeneity of MYCN-amplified medulloblastoma.Korshunov A et al
20667551991Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study.Look AT et al
164453742006MYCN deregulation as a potential target for novel therapies in rhabdomyosarcoma.Morgenstern DA et al
159750482005The MYCN oncogene as a specific and selective drug target for peripheral and central nervous system tumors.Pession A et al
192553302009Outcome prediction in pediatric medulloblastoma based on DNA copy-number aberrations of chromosomes 6q and 17q and the MYC and MYCN loci.Pfister S et al
171753812007Array comparative genomic hybridization reveals unbalanced gain of the MYCN region in Wilms tumors.Schaub R et al
182816642008Clinical significance of MYCN amplification and ploidy in favorable-stage neuroblastoma: a report from the Children's Oncology Group.Schneiderman J et al
68885611983Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour.Schwab M et al
150132172004MYCN in neuronal tumours.Schwab M et al
40471151985Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.Seeger RC et al
204789982010Pleiotropic role for MYCN in medulloblastoma.Swartling FJ et al
119207422002MYCN expression in human rhabdomyosarcoma cell lines and tumour samples.Toffolatti L et al
89961281997MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4s: the Italian experience with 295 children.Tonini GP et al
92146161997Targeted expression of MYCN causes neuroblastoma in transgenic mice.Weiss WA et al
218822822011Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.Williams RD et al
28387901988Heterogeneity of lung cancer cells with respect to the amplification and rearrangement of myc family oncogenes.Yokota J et al

Other Information

Locus ID:

NCBI: 4613
MIM: 164840
HGNC: 7559
Ensembl: ENSG00000134323


dbSNP: 4613
ClinVar: 4613
TCGA: ENSG00000134323


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202


Entity IDNameTypeEvidenceAssociationPKPDPMIDs


Pubmed IDYearTitleCitations
201737402010miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis.489
234306992013Targeting MYCN in neuroblastoma by BET bromodomain inhibition.219
191118822009Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma.171
230421162012LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression.135
185044382008The MYCN oncogene is a direct target of miR-34a.116
184880212008The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.110
224399332012Activated ALK collaborates with MYCN in neuroblastoma pathogenesis.100
235392692013Histone H3.3. mutations drive pediatric glioblastoma through upregulation of MYCN.98
230910292012Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification.90
156444442005The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma.87


Tiangang Zhuang ; Mayumi Higashi ; Venkatadri Kolla ; Garrett M Brodeur

MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian))

Atlas Genet Cytogenet Oncol Haematol. 2012-02-01

Online version:

Historical Card

1998-03-01 MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)) by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France