Evidence map›Paper›PMID 27819678›Full record

ArticleOncogene2017

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

M L Nickerson, S Das, K M Im, S Turan, S I Berndt, H Li, H Lou, S A Brodie, J N Billaud, T Zhang and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
3.7field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 76 citations in OpenAlex.

  1. Article
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  13. Article
  14. The role of TET2 in solid tumors and its therapeutic potential: a comprehensive review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Review
  15. Article
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  17. Review
  18. Review
  19. Article
  20. Identification of mHeliyon · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 7 institutions in 1 country.

M L NickersonCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
S DasProtein Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
K M ImData Science for Genomics, Ellicott City, MD, USA.
S TuranCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
S I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
H LiCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.ORCID 0000-0002-3501-4299
H LouCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
S A BrodieDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J N BillaudIngenuity Systems, Inc., Redwood City, CA, USA.
T ZhangLaboratory of Translational Genomics, National Cancer Institute, Bethesda, MD, USA.
A J BoukDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
D ButcherPathology and Histotechnology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Z WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
L SunMouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
K MisnerCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
W TanCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
A EsnakulaDepartment of Pathology, Howard University College of Medicine, Howard University Hospital, NW, Washington, DC, USA.
D EspositoProtein Expression Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
W Y HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
R N HooverDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
M A TuckerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J R KellerMouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
J BolandDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
K BrownLaboratory of Translational Genomics, National Cancer Institute, Bethesda, MD, USA.
S K AndersonCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
L E MooreDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
W B IsaacsSchool of Medicine, Johns Hopkins University, Baltimore, MD, USA.
S J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
M YeagerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
M DeanCancer and Inflammation Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.ORCID 0000-0003-2234-0631
T AndressonProtein Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
National Institutes of Health · USLeidos (United States) · USNational Cancer Institute · USAcuity Technologies (United States) · USHoward University Hospital · USID Genomics (United States) · USJohns Hopkins University · US

Funding

Molecular-Cellular Regulation of Hematopoietic Stem CellsZIABC010001 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KELLER, JONATHAN R · 2009 to 2024
$16.8M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS Z99 CA999999NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants are bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression are positively correlated in prostate tumours. TET2 is expressed in normal prostate tissue and reduced in a subset of tumours from the Cancer Genome Atlas (TCGA). Small interfering RNA-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 proximal to KLK3. A gene co-expression network identified using TCGA prostate tumour 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 signalling. Decreased TET2 mRNA expression in TCGA PCa tumours is strongly associated with reduced patient survival, indicating reduced expression in tumours may be an informative biomarker of disease progression and perhaps metastatic disease.

Indexed as

Cell ProliferationDioxygenasesDNA-Binding ProteinsHEK293 CellsHumansIntronsKallikreinsKetoglutaric AcidsMalePolymorphism, Single NucleotideProstate-Specific AntigenProstatic NeoplasmsProto-Oncogene ProteinsReceptors, AndrogenSuccinatesAR protein, humanDioxygenasesDNA-Binding ProteinsKallikreinsKetoglutaric AcidsKLK3 protein, humanProstate-Specific AntigenProto-Oncogene ProteinsReceptors, AndrogenSuccinatesTET2 protein, human

Identifiers

PMID27819678
PMCPMC5391277
OpenAlexW2553426779

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.