Evidence map›Paper›PMID 37327786›Full record

ArticleCell2023

DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and CTCs.

Hongshan Guo, Joanna A Vuille, Ben S Wittner, Emily M Lachtara, Yu Hou, Maoxuan Lin, Ting Zhao, Ayush T Raman, Hunter C Russell, Brittany A Reeves and 12 more

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

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

59 citing papers in PubMed, 67 citations in OpenAlex.

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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

22 authors at 5 institutions in 2 countries.

Hongshan GuoMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Joanna A VuilleMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Ben S WittnerMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Emily M LachtaraMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Yu HouEvergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Maoxuan LinMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ting ZhaoMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Ayush T RamanMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Hunter C RussellMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Brittany A ReevesMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
Haley M PleskowMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Chin-Lee WuMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Andreas GnirkeBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alexander MeissnerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany.
Jason A EfstathiouMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Richard J LeeMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Mehmet TonerDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Engineering in Medicine and Shriners Hospital for Children, Harvard Medical School, Boston, MA 02114, USA.
Martin J AryeeMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Michael S LawrenceMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
David T MiyamotoMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: dmiyamoto@mgh.harvard.edu.
Shyamala MaheswaranMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: maheswaran@helix.mgh.harvard.edu.
Daniel A HaberMassachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: dhaber@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USBroad Institute · USHoward Hughes Medical Institute · USShriners Hospitals for Children - Erie · US

Funding

Point-of care Microfluidics for Early Detection of CancerU01EB012493 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A., TONER, MEHMET · 2010 to 2018
$19.6M
Bio-MicroElectroMechanical Systems Resource CenterP41EB002503 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET · 2004 to 2018
$17.4M
Modeling Metastasis and Acquired Drug Resistance Using Circulating Tumor CellsR01CA129933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber · 2008 to 2026
$7.5M
Microfluidic isolation and molecular analysis of circulating tumor cells for the study of neuroendocrine transdifferentiation in prostate cancerU01CA268933 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Melissa Abel, Mehmet Toner · 2022 to 2026
$3.0M
Blood-based monitoring of bladder-sparing trimodality therapy for muscle-invasive bladder cancerR01CA259007 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MIYAMOTO, DAVID T. · 2022 to 2025
$3.0M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA129933NCI NIH HHS R01 CA259007NCI NIH HHS U01 CA268933NIBIB NIH HHS P41 EB002503NIBIB NIH HHS U01 EB012493
6 · The paper itself

Abstract

Cancer is characterized by hypomethylation-associated silencing of large chromatin domains, whose contribution to tumorigenesis is uncertain. Through high-resolution genome-wide single-cell DNA methylation sequencing, we identify 40 core domains that are uniformly hypomethylated from the earliest detectable stages of prostate malignancy through metastatic circulating tumor cells (CTCs). Nested among these repressive domains are smaller loci with preserved methylation that escape silencing and are enriched for cell proliferation genes. Transcriptionally silenced genes within the core hypomethylated domains are enriched for immune-related genes; prominent among these is a single gene cluster harboring all five CD1 genes that present lipid antigens to NKT cells and four IFI16-related interferon-inducible genes implicated in innate immunity. The re-expression of CD1 or IFI16 murine orthologs in immuno-competent mice abrogates tumorigenesis, accompanied by the activation of anti-tumor immunity. Thus, early epigenetic changes may shape tumorigenesis, targeting co-located genes within defined chromosomal loci. Hypomethylation domains are detectable in blood specimens enriched for CTCs.

Indexed as

DNA MethylationProstatic NeoplasmsAnimalsCarcinogenesisDNAEpigenesis, GeneticHumansMaleMiceNeoplastic Cells, CirculatingDNACD1Acirculating tumor cellsDNA hypomethylationIFI16immune surveillancelipid antigensNKT cellsprostate cancersingle-cell sequencingtumorigenesis

Identifiers

PMID37327786
PMCPMC10436379
OpenAlexW4380854450

What OpenQuestion holds

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LicenceCC BY
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.