CCNE1

Overview

CCNE1 encodes Cyclin E1, which partners with CDK2 to drive the G1-to-S phase transition. CCNE1 amplification is a recurrent oncogenic alteration across gynecologic, gastrointestinal, and ovarian cancers, linked to chromosomal instability, replication stress, and resistance to chemotherapy. It is particularly enriched in aggressive histologic subtypes and in minority patient populations with endometrial carcinoma.

Alterations observed in the corpus

  • Amplification more prevalent in Black patients with endometrial carcinoma (15% vs. 4% in White patients) and specifically in carcinosarcomas from Black patients (29% vs. 10%); associated with chromosomal instability and replication stress PMID:37651310.
  • Amplification enriched in early-onset esophagogastric cancer (16% vs. 7% in average-onset, P=0.001, Q=0.011), driven by the chromosomal instability esophageal/GEJ subgroup PMID:37699004.
  • Amplification noted as an early copy number alteration event in serous tubal intraepithelial carcinomas (STICs), linked to breakage-fusion-bridge cycles during high-grade serous ovarian carcinoma development PMID:39386723.
  • CCNE1 amplification used to assign patients to the foldback-inversion-enriched genomic subtype in a 444-patient HGSOC multimodal risk-stratification study; amplification status overrides concurrent HRD-DDR variant evidence per MSKCC subtype-assignment rules; copy number assessed via MSK-IMPACT pipeline (MSKCC cases) and cBioPortal download (TCGA-OV cases) PMID:35764743.
  • CCNE1 amplification reported as one of the genes appearing in volcano-plot metastasis-association analyses in the MSK-CHORD real-world cohort (n=42,655 patients) PMID:39506116.
  • Identified as mutated/amplified in LUAD (TSP, n=188); cell cycle pathway member co-altered with CDK4, CDK6, CCND1, and CDKN2A/B. PMID:18948947
  • High-level amplification associated with FBI (FHRD-BI) genomic signature in HGSOC; 29/118 patients with HLA LOH in validation cohort PMID:36517593
  • CCNE1 amplification in 2% of metastatic UC samples (UC-GENOME cohort) PMID:36333289
  • CCNE1 amplification in 9% of GBC PMID:36228155
  • Found focally amplified in ~20% of HGSOC tumors in TCGA integrated genomic analysis of ovarian carcinoma PMID:21720365
  • CCNE1 amplification detected in HNSCC by whole-exome sequencing of 74 tumor-normal pairs (Broad Institute cohort) PMID:21798893
  • Upregulated in basal-like IntClust 10 as part of a chromosome 5q deletion-associated trans-acting mitotic network in the METABRIC cohort (2,000 tumors) PMID:22522925
  • Recurrent HBV integration target (5% of HCCs); HBV-CCNE1 fusions increase cyclin E1 expression and inhibit the RB pathway, disrupting G1/S cell cycle regulation PMID:22634756
  • Altered in SCLC WES/WGS study (CLCGP, 29 tumors) alongside universal TP53/RB1 loss PMID:22941188
  • Amplified in breast cancer (TCGA, 510 tumors); CCNE1 amplification observed predominantly in basal-like and HER2-enriched subtypes, linked to replication stress and genomic instability PMID:23000897
  • Frequently focally amplified in esophageal adenocarcinoma (EAC), contributing to cell-cycle deregulation PMID:23525077
  • Focal amplification in 5% of high-grade bladder tumors; mutually exclusive with CCND1 amplification and inversely correlated with RB1 loss PMID:23897969
  • Focal amplification in bladder TCC; part of a set of recurrently amplified oncogenes alongside CCND1 and E2F3 PMID:24121792
  • Focal amplification in 12% of muscle-invasive bladder carcinomas (BLCA, n=131); part of mRNA cluster C (‘TP53/cell-cycle-mutant’) which shows near-universal TP53 mutation, RB1 mutation, and E2F3/CCNE1 amplification; GISTIC 2.0 analysis of TCGA bladder cohort PMID:24476821
  • Recurrent focal amplification in CIN gastric adenocarcinoma; suggests CDK4/6 inhibitor evaluation in this subtype PMID:25079317
  • Recurrent focal amplification in LUAD; identified as one of multiple significant amplification peaks in the TCGA lung adenocarcinoma dataset (n=230) PMID:25079552
  • Cell-cycle/RB axis alteration in HCC; CDKN2A loss enriched in alcohol-related HCC and independently associated with poor survival PMID:25822088
  • Present among tumor-suppressor candidates in desmoplastic melanoma exome sequencing cohort (n=60 discovery + 42 validation); listed as a gene with LOF-burden alteration PMID:26343386
  • CCNE1 focal amplification is significantly IDC-enriched (7% IDC vs 0% ILC, q=0.01) in the TCGA multi-platform breast cancer analysis of 817 tumors PMID:26451490
  • CCNE1 overexpression in osteosarcoma (OS) alongside MYC and MCL1 identified as BET- and CDK4/6-inhibitor targets in the PIPseq pediatric precision-oncology cohort PMID:28007021
  • CCNE1 amplified at 19q12 more often in esophageal adenocarcinoma (EAC) than in ESCC, in the TCGA multi-platform esophageal carcinoma study PMID:28052061
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Cancer types (linked)

  • UCEC/UCS: CCNE1 amplification enriched in Black patients, particularly carcinosarcomas; associated with CN-H/TP53abn molecular subtype; potential target for WEE1 inhibitors, ATR inhibitors, and PKMYT1 kinase inhibitors PMID:37651310.
  • EGC/STAD/ESCA/GEJ: Enriched in early-onset disease; may represent a therapeutic opportunity with CDK2 inhibitors PMID:37699004.
  • HGSOC: Early CNA event in STICs preceding invasive cancer; implicated in chromosomal instability through breakage-fusion-bridge cycles PMID:39386723. Amplification also defines the foldback-inversion-enriched genomic subtype in a 444-patient multimodal risk-stratification study and takes priority over HRD-DDR variant evidence in subtype assignment PMID:35764743.

Co-occurrence and mutual exclusivity

  • In endometrial carcinoma, CCNE1 amplification co-occurs with TP53 mutations in the CN-H/TP53abn molecular subtype PMID:37651310.
  • In early-onset EGC, enrichment is concentrated in the chromosomal instability esophageal/GEJ molecular subgroup PMID:37699004.

Therapeutic relevance

  • CCNE1 amplification is a candidate target for WEE1 inhibitors (e.g., adavosertib), ATR inhibitors, and PKMYT1 kinase inhibitors under clinical investigation in endometrial carcinoma PMID:37651310.
  • Enrichment in early-onset EGC may represent a therapeutic opportunity with CDK2 inhibitors PMID:37699004.

Open questions

  • Whether CCNE1 amplification functions differently in carcinosarcoma vs. endometrioid endometrial carcinoma contexts, and which inhibitor class is optimal, remains unresolved.
  • The causal role of CCNE1 amplification in early HGSOC precursor evolution versus its role as a passenger CNA has not been fully established PMID:39386723.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:18948947

This page was processed by crosslinker on 2026-05-14. - PMID:36517593

This page was processed by crosslinker on 2026-05-14. - PMID:36333289

This page was processed by crosslinker on 2026-05-14. - PMID:36228155

This page was processed by crosslinker on 2026-05-14. - PMID:21720365

This page was processed by crosslinker on 2026-05-14. - PMID:21798893

This page was processed by crosslinker on 2026-05-14. - PMID:22522925

This page was processed by crosslinker on 2026-05-14. - PMID:22634756

This page was processed by crosslinker on 2026-05-14. - PMID:22941188

This page was processed by crosslinker on 2026-05-14. - PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:23525077

This page was processed by crosslinker on 2026-05-14. - PMID:23897969

This page was processed by crosslinker on 2026-05-14. - PMID:24121792

This page was processed by crosslinker on 2026-05-14. - PMID:24476821

This page was processed by crosslinker on 2026-05-14. - PMID:25079317

This page was processed by crosslinker on 2026-05-14. - PMID:25079552

This page was processed by crosslinker on 2026-05-14. - PMID:25822088

This page was processed by crosslinker on 2026-05-14. - PMID:26343386

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

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