MYC

Overview

MYC is a master transcriptional oncogene dysregulated across many cancers through amplification, translocation, and copy-number gain.

Alterations observed in the corpus

CLL: implicated via 8q gain, a rare adverse feature in M-CLL PMID:35927489.
NSCLC brain metastases: MYC alterations enriched in LUAD primary tumors from patients who later developed BM (BM+ vs BM−/EM−) PMID:37591896.
MYC amplifications associated with multifocal regional intracranial progression (22% vs 0% in local progressors, p=0.023); MYC pathway alterations enriched in LMD (p=0.013, q=0.14) and regional progression groups PMID:37591896.
High-risk small bowel GIST class in the elastic-net Cox genomic risk model was defined by alterations in any of MAX/MGA/MYC, CDKN2A, or RB1 PMID:37477937.
MYC amplification was present in 75% of RT-ANGS (33/44), exclusively in breast/chest wall cases (87% of 38 breast cases); no RT-AS from other anatomic sites were MYC-amplified (vs 13% sporadic AS). MYC-amplified RT-AS had significantly shorter radiation-to-sarcoma latency (log-rank P=0.0083) PMID:37350195.
MYC translocation co-occurs with BCL6 translocation in BN2 DLBCL subtype (15.3%); also present at low frequency in EZB, MCD, and ST2 subtypes; classified via LymphGen on 400-gene clinical NGS panel PMID:38497151.
MYC oncogenic alterations associated with inferior PFS on multivariable analysis in HER2+ metastatic esophagogastric cancer treated with pembrolizumab + trastuzumab + chemotherapy PMID:37406106.
MYC amplifications seen in uterine endocervical adenocarcinoma (UEA, 4%) and small cell cervical carcinoma (2/5 cases, with concurrent TP53 mutations) PMID:37643132.
FOXM1 and MYC transcription factor networks enriched in MG4 (proliferative) meningioma molecular group PMID:34433969.
MYC upregulated in HLA-E+ STIC.I fallopian tube epithelium alongside the IFN/antigen-presentation program in HGSOC precursor lesions; MX1, IRF1, DDX60, OAS3, IFI44, PSMB8, XAF1 co-enriched in the same HLA-E+ regions by GeoMx WTA spatial transcriptomics. PMID:39386723
KrasG12R organoids show loss of Myc activation relative to KrasG12D organoids; MYC highlighted as a key downstream effector of KRAS allele-specific signaling in PDAC progression. PMID:39214094
MYC among additional genes appearing in volcano plots of metastasis-association analyses in the MSK-CHORD pan-cancer real-world cohort (n=52,211). PMID:39506116
In the MSK 2,336-patient PDAC cohort, actionability landscape includes OncoKB-annotated MYC-pathway genes among emerging targets; MYC-driven transcriptional programs listed as key PDAC oncogenic mechanisms. PMID:39753968
Copy number amplifications enriched in breast cancer metastases compared to primary tumors PMID:36585450
Amplification associated with expected gene dosage effects in HGSOC genomic analysis PMID:36517593
MYC amplification detected at resistance to KRASG12C + EGFR inhibition in CRC patient ctDNA PMID:36355783
MYC amplification in 7% of GBC (oncogenic CNA) PMID:36228155
MYC was among recurrently amplified oncogenes in prostate cancer identified by integrative genomic profiling of the MSKCC cohort PMID:20579941
MYC amplification at 8q24 was identified as a significant copy-number alteration in HGSOC by TCGA integrated genomic analysis PMID:21720365
Identified as a significantly mutated gene in HNSCC whole-exome sequencing of 74 tumor-normal pairs (Broad cohort) PMID:21798893
BET bromodomain inhibition suppresses MYC transcription in ARID1A-mutant ovarian cancer models PMID:22037554
MYC copy number alterations were assessed in breast cancer samples as part of whole-exome sequencing that identified SF3B1 mutations and splicing dysregulation PMID:22158541
MYC amplification is a key driver in breast cancer, enriched in high-proliferation IntClust subtypes of the METABRIC cohort (~2,000 tumors) PMID:22522925
Mutated in >10% of cases in breast cancer WES (100 tumors, Sanger cohort); identified as a high-frequency driver gene PMID:22722201
Amplification in subgroup-3 medulloblastoma (PCGP WGS, 37 tumors); mutually exclusive with epigenetic mutations (KDM6A, CHD7, ZMYM3) PMID:22722829
Transcriptional activator of the miR-17-92 cluster; expression correlated (r = 0.61) with miR-18a across NCI-60 cell lines in CellMiner pharmacogenomics platform analysis PMID:22802077
Amplification at 8q24 in colorectal cancer (276-tumor TCGA CRC cohort); transcriptional targets universally altered per PARADIGM pathway analysis PMID:22810696
MYC broad amplicon on chromosome 8q in 23% (17/74) of colorectal cancer tumors PMID:22895193
MYC focal amplification in SCLC (rare, 1 case); mutually exclusive with MYCL and MYCN amplification (CLCGP, 29 tumors) PMID:22941188
MYC copy-number amplification identified in SCLC (JHU WES/WGS, 36 tumors) PMID:22941189
MYC amplification identified as a recurrent somatic copy-number alteration in lung squamous cell carcinoma (TCGA, 178 tumors) PMID:22960745
MYC pathway alterations identified in lung adenocarcinoma (Broad WES, 183 tumors) PMID:22980975
Copy-number amplification across breast cancer subtypes; hyperactivation characteristic of Basal-like breast cancer (TCGA, 510 tumors) PMID:23000897
Focal amplification observed in ≥5% of OSCC tumors (8q gain); part of the mitogenic signaling pathway altered in 63% of OSCC tumors (40-tumor MD Anderson cohort) PMID:23619168
Focal amplification at 8q24.12 in the copy-number-high (serous-like) cluster-4 endometrial carcinoma subgroup, which shares molecular features with high-grade serous ovarian carcinoma (TCGA 373-tumor cohort) PMID:23636398
Focal amplification identified in clear cell renal cell carcinoma (ccRCC) by TCGA comprehensive molecular characterization PMID:23792563
Recurrent focal amplification in GBM; subtype-correlated amplification pattern noted across GBM transcriptomic subtypes PMID:24120142
Focal amplification identified in TCC bladder cancer (UCGC cohort, n=99) PMID:24121792
Amplified in ovarian MiNEN patient PN19; Cluster B transcriptome signature showed enrichment of MYC-target gene sets and MYC-family activation by master-regulator analysis; MYC-amplified NENs flagged as highly aggressive and chemo-resistant PMID:24326773
Dysregulated in multiple myeloma through disruption of the MAX-MYC heterodimer axis; MAX coding mutations with LOH implicate MYC-axis oncogenic signaling PMID:24434212
MYC focal amplification observed in ESCC tumors PMID:24686850
MYC gains at 8q are observed in HCC as a recurrent copy-number alteration PMID:24735922
Focal amplification in ~12% of HCCs; co-occurs with CCND1 amplification (7%) as recurrent copy-number gains driving proliferation in the HCC proliferation subclass PMID:24798001
MYC focal copy number gain in prostate cancer; not significantly associated with biochemical recurrence in this CNA-burden study PMID:25024180
MYC focal amplification in CIN subtype of gastric cancer (EGC); co-amplified with GATA4, GATA6, ZNF217, CD44 PMID:25079317
MYC 8q24 amplification peak in LUAD (TCGA, n=230); overexpression associated with CIMP-H methylation phenotype (P=0.003); mutually exclusive with MGA loss-of-function mutations (P=0.04) PMID:25079552
MYC enriched among large-duct-type intrahepatic CCA, defining a molecular subtype with distinct biology PMID:25526346
MYC recurrently mutated driver in gastric adenocarcinoma; participates in Wnt, PI3K-ERBB, and TP53 pathways in this Chinese cohort (n=294) PMID:25583476
MYC amplified in 10/29 (34%) metastatic cSCC samples (one high-level); part of recurrent copy-number gains alongside TP63, CCND1, LAMA5. PMID:25589618
MYC amplified in 14% HPV(−) and 3% HPV(+) HNSC (TCGA, n=279); MYC was not the target of HPV integration in this cohort (contradicting prior cell-line reports). PMID:25631445
In HCC, MYC is recurrently amplified. PMID:25822088
In pancreatic ductal adenocarcinoma (PAAD), MYC focal amplification at 8q24.13 is uniquely associated with poor overall survival (P=0.0013) and adenosquamous histology (PAASC); detectable in PanIN precursor lesions; confirmed by break-apart FISH. PMID:25855536
In mCRPC, MYC is among recurrent CNAs (8q gain) identified in the 150-patient SU2C–PCF prospective cohort. PMID:26000489
Recurrent focal amplification in SCLC PMID:26168399
Upregulated at mRNA and protein level in SF3B1-mutant/del(13q) CLL cells; mTORC1 activation drives MYC upregulation; pathway enrichment confirmed by GSEA in murine and human CLL PMID:26200345
Focal amplification in 1-3 desmoplastic melanoma tumors PMID:26343386
Focal amplification of MYC is IDC-enriched relative to ILC in TCGA breast cancer molecular profiling; MYC amplification rate is higher in invasive ductal carcinoma than in invasive lobular carcinoma PMID:26451490
Recurrent focal amplification in 8% of prostate adenocarcinoma tumors in the TCGA cohort (n=333) PMID:26544944
MYC locus chromothripsis acquired only at recurrence in medulloblastoma case MB-REC-09 (P=3.97x10-7), illustrating de novo oncogene activation as a recurrence mechanism in Shh-subgroup medulloblastoma PMID:26760213
Putative MYB target gene in ACC; among downstream targets identified in super-enhancer-driven MYB regulatory program PMID:26829750
MYC shows recurrent 8q copy gain in metastatic castration-resistant prostate cancer (mCRPC) rapid-autopsy cohort; gain is largely shared across metastases within a patient PMID:26928463
MYC amplification observed as a copy-number alteration in pan-lung cancer TCGA analysis (n=1144) PMID:27158780
MYC driver copy-number amplification at 8q24 defines IntClust9 in breast cancer; used in the IntClust copy-number taxonomy PMID:27161491
Novel hotspot mutations described in the AML cohort (Supplementary Results S1) PMID:27276561
Transcriptional-regulator gene with mutations enriched in the DUX4/ERG B-ALL subtype (IGH–DUX4 rearrangement) relative to 209 other B-ALL and 16 T-ALL comparator cases PMID:27776115
Recurrent MYC amplification in metastatic breast cancer (mBC), consistent with findings in primary breast cancer PMID:28027327
MYC amplification more common in EAC than CIN gastric adenocarcinoma; identified as a recurrent somatic amplification in esophageal adenocarcinoma PMID:28052061
Referenced as a known SCLC oncogene contributing to transcriptional addictions and super-enhancer biology in acquired chemoresistance study (EZH2/SLFN11 axis in SCLC) PMID:28196596
Recurrent oncogene amplification in cholangiocarcinoma (n=12 WGS cases) PMID:28667006
Amplification restricted to Group 3 medulloblastoma (17% of Group 3 cases) in genome-wide analysis of 491 medulloblastomas PMID:28726821
MYC was identified as a functional oncogene in DLBCL by CRISPR screen (depletion on knockout); MYC mutations were strongly associated with poorer overall survival (p<0.05); MYC translocations correlated with high MYC expression; high MYC expression combined with high BCL2 expression (double expressors) defined the poorest prognosis subgroup; MYC genetic alterations combined with high MYC expression defined the least favorable prognosis subgroup in a multivariate genomic model PMID:28985567

Cancer types (linked)

CLLSLL — rare adverse 8q gain in M-CLL PMID:35927489.
LUAD / NSCLC — enriched in brain-metastatic primaries and linked to multifocal regional intracranial progression PMID:37591896.
ANGS — MYC amplification in 75% of RT-AS (breast/chest wall), defining the dominant genomic event in radiation-associated angiosarcoma; co-occurs with FLT4, CRKL, HRAS, and KMT2D PMID:37350195.

Co-occurrence and mutual exclusivity

In RT-ANGS, MYC amplification co-occurs with FLT4, CRKL, HRAS, and KMT2D alterations PMID:37350195.

Therapeutic relevance

MYC amplification may flag NSCLC patients at risk for multifocal regional intracranial progression, informing CNS surveillance/therapy strategy PMID:37591896.
Single-cell RNA sequencing of pre- and post-RT PBMCs in the ROBIN ImmunoRad MCT identified MYC-driven transcriptional activation in CD8+ T cells following radiotherapy, consistent with systemic immune reprogramming and the concept of trained immunity PMID:41941260.

Open questions

Whether MYC-amplified NSCLC brain metastases respond differently to available systemic therapy is not resolved PMID:37591896.
The mechanism underlying the exclusive association of MYC amplification with breast/chest wall RT-AS (and not other anatomic sites) remains unclear PMID:37350195.

Sources

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