Biomarker: TET1

Histology type: endometrial carcinoma

Country: China

Region: Taipei

Study type: retrospective study

Followed up time :

Subgroup 1 name : TET1<20

Subgroup 1 number: 44

Subgroup 2 name: TET1 high>20

Subgroup 2 number: 42

Conclusion: Loss of ten-eleven translocation 1 (TET1) expression as a diagnostic and prognostic biomarker of endometrial carcinoma

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : lower score (≤20)

Expression elevation: The immunoreactivity was graded arbitrarily and semiquantitatively by considering the intensity and percentage of staining on the tissue microarray slides as described previously [23]. The intensity of 5-hmC, 5-mC, and TET1 staining in individual tumor cells was scored as 0 (no staining), 1+ (weak intensity), 2+ (moderate intensity), or 3+ (strong intensity). The percentage of cells for each intensity was estimated from 0 to 100. For semiquantitative analysis of these three markers’ expression, the absolute score was calculated by multiplying the estimated percentage of stained cells at each intensity by the corresponding intensity value, which produced an immunostaining score from 0 to 300. The optimal cut-off value was determined using a receiver-operating characteristic (ROC) curve. TET1low was defined as a score ≤ 20, and TET1high was defined as a score >20; 5-hm Clow was defined as a score ≤80, and 5-hmChigh was defined as a score >80; whereas 5-mClow was defined as a score ≤270, and 5-mChigh was defined as a score >270.

Statictics: Range

Cohort age: 31-88

Funtion Uniprot: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation (PubMed:19372391, PubMed:21496894). Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC) (PubMed:21778364). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression (PubMed:33833093). Plays therefore a role in many biological processes and diseases, including stem cell maintenance, T and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair (PubMed:31278917). Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis (PubMed:25284789). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034). Plays an essential role in the protection and maintenance of transcriptional and developmental programs together with QSER1 to inhibit the binding of DNMT3A/3B and therefore de novo methylation (PubMed:33833093).

UniProt ID: Q8NFU7

UniProt Link: https://www.uniprot.org/uniprotkb/Q8NFU7/entry

Biological function from UniProt: Transcription, Transcription regulation

Molecular function from UniProt:

Tissue specificity from UniProt: Expressed in fetal heart, lung and brain, and in adult skeletal muscle, thymus and ovary. Not detected in adult heart, lung or brain. Up-regulated in glioblastoma cells (at protein level) (PubMed:25284789).

Subcellular UniProt: #Chromosome #Nucleus

Alternative name from UniProt:

Caution: Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system (PubMed:21496894). According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG and replacement by unmethylated cytosine

Catalytic activity: 2-oxoglutarate + a 5-methyl-2'-deoxycytidine in DNA + O2 = a 5-hydroxymethyl-2'-deoxycytidine in DNA + CO2 + succinate,2-oxoglutarate + a 5-hydroxymethyl-2'-deoxycytidine in DNA + O2 = a 5-formyl-2'-deoxycytidine in DNA + CO2 + H2O + succinate,2-oxoglutarate + a 5-hydroxymethyl-2'-deoxycytidine in DNA + O2 = a 5-formyl-2'-deoxycytidine in DNA + CO2 + H2O + succinate.

Recommended name: Methylcytosine dioxygenase TET1

Gene name from HGNC: TET1 (bA119F7.1, CXXC6, KIAA1676, LCX)

HPA class: Cancer-related genes Disease related genes Enzymes Potential drug targets Transcription factors

AlphaFold DB: Q8NFU7

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q8NFU7

HPA link: https://www.proteinatlas.org/ENSG00000138336-TET1

Tissue specificity RNA from HPA: Tissue enhanced (brain)

Single cell type specificity Cell type enhanced (Extravillous trophoblasts, Astrocytes, Oligodendrocytes, Oligodendrocyte precursor cells, Theca cells)

Immune cell specificity: Not detected in immune cells

Subcellular summary HPA Located in Nucleoplasm, Nuclear membrane

Cancer prognostic summary HPA Gene product is not prognostic

Pathology link: https://www.proteinatlas.org/ENSG00000138336-TET1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000138336-TET1/pathology/endometrial+cancer

Expression figure legend: TET1 expression in samples of normal endometrium (A1), EH without atypia (B1), AH (C1), G1 of EmAC (D1), G2 of EmAC (E1), G3 of EmAC (F1), SC (G1), MC (H1), and CC (I1);

Expression figure link: https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0259330.g001

Disease: No disease ID

Note1: A chromosomal aberration involving TET1 may be a cause of acute leukemias (PubMed:12646957). Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1 3' (PubMed:12124344, PubMed:12646957)

OMIM: # 202200

OMIM link2: https://www.omim.org/entry/202200

HGNC ID: HGNC:29484

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:29484