Evidence map›Paper›PMID 26890396›Full record

ArticleEpigenetics2016

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

Brittany Kleb, Marcos R H Estécio, Jiexin Zhang, Vassiliki Tzelepi, Woonbok Chung, Jaroslav Jelinek, Nora M Navone, Salahaldin Tahir, Victor E Marquez, Jean-Pierre Issa and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

44 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
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  3. Game of clones: decipher lineage plasticity in hormone-driven cancers.Cellular and molecular life sciences : CMLS · 2026
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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

12 authors at 4 institutions in 2 countries.

Brittany Kleba Department of Genitourinary Medical Oncology Unit 1374 , The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
Marcos R H Estéciob Department of Epigenetics and Molecular Carcinogenesis , Unit 0081, The University of Texas, MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
Jiexin Zhangc Department of Bioinformatics and Computational Biology , Unit 1410, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
Vassiliki Tzelepid Department of Pathology , University of Patras, Panepistimioupoli Patron , Greece.
Woonbok Chunge Fels Institute of Cancer Research and Molecular Biology, Temple University , 3307 N Broad Street, Philadelphia , PA.
Jaroslav Jelineke Fels Institute of Cancer Research and Molecular Biology, Temple University , 3307 N Broad Street, Philadelphia , PA.
Nora M Navonef Department of Genitourinary Medical Oncology , Unit 1374, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
Salahaldin Tahirf Department of Genitourinary Medical Oncology , Unit 1374, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
Victor E Marquezg Center for Cancer Research, National Cancer Institute, Building 376 Frederick , MD.
Jean-Pierre Issae Fels Institute of Cancer Research and Molecular Biology, Temple University , 3307 N Broad Street, Philadelphia , PA.
Sankar Maityf Department of Genitourinary Medical Oncology , Unit 1374, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
Ana Apariciof Department of Genitourinary Medical Oncology , Unit 1374, The University of Texas MD Anderson Cancer Center , 1515 Holcombe Blvd., Houston , Texas.
The University of Texas MD Anderson Cancer Center · USTemple University · USFrederick National Laboratory for Cancer Research · USUniversity of Patras · GR

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
Targeting Tumor Microenvironment-Induced Therapy Resistance in Prostate Cancer Bone MetastasisP50CA140388 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LOGOTHETIS, CHRISTOPHER J., THOMPSON, TIMOTHY CHARLES · 2009 to 2022
$23.4M
NCI NIH HHS P30 CA006927NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA140388
6 · The paper itself

Abstract

Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

Indexed as

AdenosineAnimalsCarcinoma, Small CellCell LineageCell Line, TumorCpG IslandsDNA MethylationEnhancer of Zeste Homolog 2 ProteinGene Expression Regulation, NeoplasticHumansMaleMicePromoter Regions, GeneticProstatic Neoplasms, Castration-ResistantReceptors, AndrogenXenograft Model Antitumor Assays3-deazaneplanocinAdenosineEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanReceptors, AndrogenAndrogen receptorDNA methylationepigeneticsEZH2histone methylationneuroendocrineprostate cancersmall-cell prostate carcinomaxenograft

Identifiers

PMID26890396
PMCPMC4854553
OpenAlexW2288055189

What OpenQuestion holds

Textmetadata
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.