Biomarker: CCNE1

Biomarker subtype: gene

Clinical application: treatment(theranostic target)

Histology type: endometrioid endometrial carcinoma

Country: Japan

Region: Izumo

Followed up time : 5 to 139 month months, with a median of 52 months

Cohort age: 106;54

Protocol age: 54;47

Control age: 52;7

Sample type : tissue

Clinical method: immunohistochemistry/FISH

Expression pattern : amplification

Validation in cell line : The human endometrial carcinoma cell lines HEC251 (endometrioid endometrial carcinoma ), HEC50B (endometrioid endometrial carcinoma G3), and HEC108 (endometrioid carcinoma)

Validation in cell method : Western blot ,siRNA-mediated knockdown of CCNE1 gene expression,Cell proliferation assay

Statictics: cutoff<60;cutoff>60

Cohort age: 106;54

Protocol age: 54;47

Control age: 52;7

Description: CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid endometrial carcinoma having CCNE1 amplification.

Survival figure legend: CCNE1 amplification is correlated with shorter progression-free/overall survival in patients with endometrial endometrioid carcinoma.

Survival curve link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725452/figure/f2-ijo-48-02-0506/?report=objectonly

Expression figure legend: CCNE1 amplification.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725452/figure/f1-ijo-48-02-0506/?report=objectonly

Funtion description: CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown were dependent on the CCNE1 expression status, suggesting that CCNE1-targeted therapy may be beneficial for patients with endometrial endometrioid carcinoma having CCNE1 amplification.

Approved symbol: CCNE1

Approved name: cyclin E1

Locus type: gene with protein product

HGNC ID: HGNC:1589

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1589

Symbol status: Approved

Previous symbols: CCNE

OMIM: 123837

Omim link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1589

NCBI name: 898

NCBI link: https://www.ncbi.nlm.nih.gov/gene/898

Summary: The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. [provided by RefSeq, Apr 2016]

Expression: Biased expression in placenta (RPKM 16.5), bone marrow (RPKM 11.3) and 12 other tissues

NCBI gene expression https://www.ncbi.nlm.nih.gov/gene/898#gene-expression

PDB ID: P24864

PDB link: https://www.ebi.ac.uk/pdbe/entry/search/index/?searchParams=%7B%22q_uniprot%22:%5B%7B%22value%22:%22(P24864)%22,%22condition1%22:%22AND%22,%22condition2%22:%22Contains%22%7D%5D,%22resultState%22:%7B%22tabIndex%22:0,%22paginationIndex%22:1,%22perPage%22:%2210%22,%22sortBy%22:%22Sort%20by%22%7D%7D

CC term ID: GO:0097134

CC term name: cyclin E1-CDK2 complex

Source description: REAC|CORUM

Term ID: REAC:R-HSA-69200|CORUM:5560

Term name: Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes|CDK2-CCNE1 complex