Biomarker: cyclin D1

Histology type: endometrial stromal tumor

Stage: high-grade

Country: Canada

Region: Toronto

Followed up time :

Conclusion: Our findings indicate that cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22 ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : positive expression(Tumors showing ≥ 70% moderate to strong nuclear staining for cyclin D1 were considered to be positive)

Expression elevation: Only nuclear staining was considered positive. Strong cyclin D1 staining was defined as having the same intensity as cyclin D1-positive mantle cell lymphoma control, moderate as definite staining that is visible at low power (4x objective) but weaker than cyclin D1-positive mantle cell lymphoma control, and weak as nuclear staining that require high power (20-40x) examination to recognize. Percentage of nuclei showing moderate to strong nuclear cyclin D1 staining was assessed by evaluating representative high-power fields (for whole tissue sections) or the entire tissue microarray cores. Tumors showing ≥ 70% moderate to strong nuclear staining for cyclin D1 were considered to be positive.

Funtion Uniprot: Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G1/S transition (PubMed:1833066, PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162, PubMed:33854235). Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase (PubMed:1833066, PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162). Hypophosphorylates RB1 in early G1 phase (PubMed:1833066, PubMed:1827756, PubMed:8114739, PubMed:8302605, PubMed:19412162). Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals (PubMed:1833066, PubMed:1827756, PubMed:8302605, PubMed:19412162). Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity (PubMed:15241418). Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (PubMed:9106657). Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner (PubMed:16569215, PubMed:18417529).

UniProt ID: P24385

UniProt Link: https://www.uniprot.org/uniprotkb/P24385/entry

Biological function from UniProt: #Cell cycle #Cell division #DNA damage #Transcription #Transcription regulation

Molecular function from UniProt:

Subcellular UniProt: #Cytoplasm #Membrane #Nucleus

Alternative name from UniProt:

Recommended name: G1/S-specific cyclin-D1

Gene name from HGNC: CCND1 (BCL1, D11S287E, PRAD1, U21B31)

HPA class: Cancer-related genes Disease related genes FDA approved drug targets Human disease related genes

AlphaFold DB: P24385

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/P24385

HPA link: https://www.proteinatlas.org/ENSG00000110092-CCND1

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Cytoplasmic and nuclear expression in several tissues.

Single cell type specificity Cell type enhanced (Pancreatic endocrine cells, Ductal cells, Basal respiratory cells, Urothelial cells)

Immune cell specificity: Immune cell enhanced (myeloid DC)

Subcellular summary HPA Located in Nucleoplasm (Single cell variability, CCD Protein)

Cancer prognostic summary HPA Prognostic marker in pancreatic cancer (unfavorable) and head and neck cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000110092-CCND1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000110092-CCND1/pathology/endometrial+cancer

Expression figure legend: Cyclin D1 immunostaining in the low-grade spindle cell component of YWHAE-FAM22 ESS. $Cyclin D1 immunostaining in JAZF1 ESS. $Representative images of cyclin D1 immunostaining in other uterine tumor.

Expression figure link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444748/figure/F2/$ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444748/figure/F3/$https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444748/figure/F5/

Phenotype ID: 254500

Disease: No disease ID;No disease ID;

Note1: A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle;A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer;The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving CCND1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus;

Note2: A number sign (#) is used with this entry because several chromosome aberrations, including recurrent translocations and deletions, have been found to be related to the development or progression of multiple myeloma; see CYTOGENETICS section.

OMIM: 168461;254500;

OMIM link1: https://www.omim.org/entry/254500

OMIM link2: https://www.omim.org/entry/168461;

Phenotype: Multiple myeloma

HGNC ID: HGNC:1582

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1582