Ten‐Eleven‐Translocation 2 (<scp>TET</scp>2) is downregulated in myelodysplastic syndromes

Scopim-Ribeiro, Renata; Machado-Neto, João Agostinho; Campos, Paula de Melo; Silva, Cleide Aparecida Moreira; Favaro, Patrícia; Lorand-Metze, Irene; Costa, Fernando Ferreira; Saad, Sara Teresinha Olalla; Traina, Fabı́ola

doi:10.1111/ejh.12445

Cited by 19 publications

(25 citation statements)

References 18 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was shown that TET2 mutations were associated to low 5-hmC counts in DNA. However, Liu et al (2013) [32] demonstrated that TET2 expression decreased in adult patients with MDS regardless of the mutational status, and that expression was positively correlated with 5-hmC value of total DNA [32,33]. In this study we confirmed and produced further evidence of these findings in RCC, one subtype of pediatric MDS.…”

Section: Discussionsupporting

confidence: 68%

TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood

et al. 2015

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 68%

TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood

et al. 2015

View full text Add to dashboard Cite

“…25,26 We re-examined normalized mRNA expression in a recent PCa study 9 of 29 matched normal adjacent tissue (NAT) samples, 131 primary tumors, and 19 metastatic tumors. Expression decreased when comparing the NAT with primary tumors but not significantly, but was significant when comparing primary with metastatic tumors (p = 0.01; Figure 2a).…”

Section: Resultsmentioning

confidence: 99%

TET2 binds the androgen receptor and loss is associated with prostate cancer

Nickerson

Das

et al. 2016

Oncogene

View full text Add to dashboard Cite

Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumor genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumors in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5–15% of myeloid, kidney, colon and prostate cancers. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We performed fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identified six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants were bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression were positively correlated in prostate tumors. TET2 is expressed in normal prostate tissue and reduced in a subset of tumors from the Cancer Genome Atlas (TCGA). Small interfering RNA (siRNA)-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration, and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine (hmC) proximal to KLK3. A gene co-expression network identified using TCGA prostate tumor RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signaling. Decreased TET2 mRNA expression in TCGA PCa tumors is strongly associated with reduced patient survival indicating reduced expression in tumors maybe an informative biomarker of disease progression and perhaps metastatic disease.

show abstract

“…Somatic TET2 mutations have been described in approximately 5% of older individuals without hematologic malignancy (27). However, TET2 mutations have clearly been linked to myeloid dysfunction (28) and clonal disease (29), and, more importantly, responsiveness to hypomethylating agents such as azacitabine or decitabine (30). …”

Section: Discussionmentioning

confidence: 99%

Jumping translocations in myelodysplastic syndromes

et al. 2016

View full text Add to dashboard Cite

Jumping translocations (JT) have been identified in numerous malignancies, including leukemia, but infrequently in patients with myelodysplastic syndromes (MDS). The responsible genetic region has been mapped to the JTB gene at 1q21, but breakpoints involving other chromosomal loci, such as 3q and 11q, have been described as well. We have characterized the pathological and mutational landscape, and the clinical course of 6 new MDS patients with jumping mutations using chromosome genomic array testing (CGAT) and target gene panel next generation sequencing. In addition, we have performed a literature review for other MDS cases with JTs as defined by ISCN 2013. Results support the concept that MDS in patients with jumping translocations has a poor prognosis with a high risk of progression to leukemia, and suggest that these patients warrant aggressive therapy, including HCT, early in the disease course.

show abstract

Ten‐Eleven‐Translocation 2 (TET2) is downregulated in myelodysplastic syndromes

Cited by 19 publications

References 18 publications

TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood

TET2 expression level and 5-hydroxymethylcytosine are decreased in refractory cytopenia of childhood

TET2 binds the androgen receptor and loss is associated with prostate cancer

Jumping translocations in myelodysplastic syndromes

Contact Info

Product

Resources

About