MYCN

Overview

MYCN encodes a MYC-family transcription factor; focal amplification is a recurrent oncogenic event in neuroblastoma and a subset of gliomas.

Alterations observed in the corpus

  • Focal MYCN amplifications (along with CDK4 and PDGFRA) were used to define “molecular grade-intermediate” in 1p19q intact IDH-mutant astrocytomas in a 128-patient MSKCC active-surveillance cohort PMID:37910594.
  • MYCN amplifications and missense mutations in 22% of fusion-positive rhabdomyosarcoma (FP-RMS); correlated with worse OS (p=0.0012) and worse PFS; high MYCN mRNA expression confirmed by RNA-seq; present at diagnosis as a secondary event PMID:37730754.
  • Elevated MYCN expression in neuroendocrine prostate cancer (NEPC) patient-derived xenografts without gene amplification; linked to DDR and neuroendocrine differentiation via MYCN-CDK5-RB1-E2F1 axis; AURKA co-elevated PMID:38488813.
  • MYCN amplification found in 5 of 11 neuroblastoma tumors studied by snRNA-seq; MYCN is highly expressed and significantly over-expressed in the undifferentiated high-risk nC3 cluster; MYCN amplification and/or 11q deletion define the high-risk cases in this cohort PMID:34493726.
  • RNAscope ISH in a MYCN-amplified high-risk tumor (K10) showed MYCN co-expressed with ALK and NTRK2 in discrete intratumoral regions, illustrating spatial heterogeneity at the single-cell level PMID:34493726.
  • MYCN amplification was a central focus of neuroblastoma proteomics profiling by LC-MS/MS, revealing downstream protein-level consequences of MYCN-driven transcriptional programs PMID:22367537
  • Amplification (including via chromothripsis) in subgroup-3/4 medulloblastoma (PCGP WGS, 37 tumors); co-occurs with OTX2 amplification PMID:22722829
  • Amplified in 5 SHH-subgroup medulloblastoma cases in WGS/WES of 125 tumors (ICGC cohort) PMID:22832583
  • MYCN focal amplification in 6% of SCLC tumors (CLCGP, 29 tumors); mutually exclusive with MYCL and MYC amplification PMID:22941188
  • Recurrent p.Phe44Leu point mutation in 1.7% (4/240) of non-amplified neuroblastoma cases (Broad); highly conserved residue with predicted functional impact; MYCN amplification is mutually exclusive with ATRX loss PMID:23334666
  • Recurrent focal amplification in GBM; subtype-correlated amplification pattern observed in TCGA GBM 2013 multi-platform analysis (n=543) PMID:24120142
  • Amplified in a previously characterized pancreatic NEN; mentioned as a Cluster B driver alongside MYC in a WGTA study of rare metastatic neuroendocrine neoplasms PMID:24326773
  • Recurrent focal amplification in SCLC; member of the MYC family amplified in SCLC alongside MYC and MYCL PMID:26168399
  • Focal amplification in ~18% (10/56) of a high-risk neuroblastoma WGS cohort; mutually exclusive with TERT rearrangements and ATRX mutations; MYCN amplification transcriptionally activates TERT (TERT is top hit upon MYCN knockdown in IMR5/75) and is functionally interchangeable with TERT rearrangement as a route to telomerase activation PMID:26466568
  • Over-expressed in CRPC-NE (P < 10⁻⁴); included in NEPC classifier; divergent allelic states across metastatic sites in patient WCMC7520; down-regulated by EZH2 inhibitor GSK343 in NCI-H660 PMID:26855148
  • Amplification in 5 patients (all cisplatin resistant); transcriptionally targets both TP53 and MDM2; predicts MDM2-inhibitor sensitivity by analogy to neuroblastoma in TP53-wild-type GCT PMID:27646943
  • MYCN amplification with 1p/11q LOH, 17q gain, and MYCN overexpression used in neuroblastoma (NBL) for risk-based therapy stratification across four patients in a pediatric precision-oncology cohort PMID:28007021
  • Amplification found in Group 3 (5%) and Group 4 (6%) medulloblastoma at comparable frequencies in genome-wide analysis of 491 medulloblastomas PMID:28726821

Cancer types (linked)

  • ASTR / DIFG — focal amplification marks intermediate molecular grade in IDH-mutant astrocytoma PMID:37910594.
  • Rhabdomyosarcoma (FP-RMS) — amplifications/missense mutations in 22%; correlated with worse OS (p=0.0012) and PFS PMID:37730754.
  • Prostate cancer (NEPC) — overexpressed without amplification; MYCN-CDK5-RB1-E2F1 axis drives neuroendocrine differentiation PMID:38488813.
  • NBL — amplified in 5/11 tumors; over-expressed in undifferentiated nC3 high-risk cluster; co-expressed with ALK, NTRK2, BRCA1, BRCA2 in nC3 cells; correlated with 11q deletion and 17q gain PMID:34493726.

Co-occurrence and mutual exclusivity

  • In FP-RMS, MYCN frequently co-amplified with CDK4 at the 12q13-15 locus; combined MYCN + CDKN2A alterations have additive prognostic impact (p=0.0017 for combined population) PMID:37730754.
  • In NEPC, MYCN co-elevated with AURKA (without genomic amplification), suggesting transcriptional or post-translational regulation PMID:38488813.
  • In neuroblastoma, MYCN co-amplified/co-expressed with ALK and NTRK2 in the undifferentiated nC3 cluster; this cluster also shows recurrent 17q gains and 1p/11q losses PMID:34493726.

Therapeutic relevance

  • PARP inhibition may impair MYCN-CDK5-RB1-E2F1-mediated neuroendocrine differentiation in NEPC, supporting investigation of PARP inhibitors PMID:38488813.
  • MYCN amplification/mutation in FP-RMS identifies high-risk patients; liquid biopsy (ctDNA) can detect MYCN alterations at diagnosis and relapse PMID:37730754.

Open questions

  • Whether MYCN amplification should upgrade IDH-mutant LGG molecular grade is unresolved PMID:37910594.
  • The putative lineage link between the postnatal hC1 progenitor and the MYCN-high nC3 cluster is based on transcriptional similarity and RNA velocity, not lineage tracing PMID:34493726.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:22367537

This page was processed by entity-page-writer on 2026-05-15. - PMID:22722829

This page was processed by entity-page-writer on 2026-05-15. - PMID:22832583

This page was processed by entity-page-writer on 2026-05-15. - PMID:22941188

This page was processed by entity-page-writer on 2026-05-15. - PMID:23334666

This page was processed by entity-page-writer on 2026-05-15. - PMID:24120142

This page was processed by entity-page-writer on 2026-05-15. - PMID:24326773

This page was processed by entity-page-writer on 2026-05-15. - PMID:26168399

This page was processed by entity-page-writer on 2026-05-15. - PMID:26466568

This page was processed by entity-page-writer on 2026-05-15. - PMID:26855148

This page was processed by entity-page-writer on 2026-05-15. - PMID:27646943

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by entity-page-writer on 2026-05-15. - PMID:28726821

This page was processed by wiki-cli on 2026-05-15.