Evidence map›Paper›PMID 26304549›Full record

ArticleNucleic acids research2015

DREAMing: a simple and ultrasensitive method for assessing intratumor epigenetic heterogeneity directly from liquid biopsies.

Thomas R Pisanic, Pornpat Athamanolap, Weijie Poh, Chen Chen, Alicia Hulbert, Malcolm V Brock, James G Herman, Tza-Huei Wang

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

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 15% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Cholangiocarcinoma: The era of liquid biopsy.World journal of gastroenterology · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Epialleles and epiallelic heterogeneity in hematological malignancies.Medical oncology (Northwood, London, England) · 2022
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 2 institutions in 2 countries.

Thomas R PisanicJohns Hopkins Institute for NanoBioTechnology, Baltimore, MD 21218, USA.
Pornpat AthamanolapDepartment of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Weijie PohCancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Chen ChenCancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
Alicia HulbertCancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
Malcolm V BrockCancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
James G HermanCancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA hermanj3@upmc.edu.
Tza-Huei WangJohns Hopkins Institute for NanoBioTechnology, Baltimore, MD 21218, USA Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA Cancer Biology Program, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA thwang@jhu.edu.
Sidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · US

Funding

ValidationU54CA151838 · NCI · JOHNS HOPKINS UNIVERSITY · PI POMPER, MARTIN G, SEARSON, PETER C · 2010 to 2014
$11.9M
Multiplexed Detection of Cell Free DNA Biomarkers for CancerR01CA155305 · NCI · JOHNS HOPKINS UNIVERSITY · PI WANG, TZA-HUEI JEFF · 2011 to 2015
$1.7M
Digital Detection of Tumor-Derived Circulating Methylated DNAR21CA186809 · NCI · JOHNS HOPKINS UNIVERSITY · PI WANG, TZA-HUEI JEFF · 2014 to 2016
$698k
NCI NIH HHS R01 CA155305NCI NIH HHS R01CA155305NCI NIH HHS R21 CA186809NCI NIH HHS R21CA186809NCI NIH HHS U54 CA151838NCI NIH HHS U54CA151838
6 · The paper itself

Abstract

Many cancers comprise heterogeneous populations of cells at primary and metastatic sites throughout the body. The presence or emergence of distinct subclones with drug-resistant genetic and epigenetic phenotypes within these populations can greatly complicate therapeutic intervention. Liquid biopsies of peripheral blood from cancer patients have been suggested as an ideal means of sampling intratumor genetic and epigenetic heterogeneity for diagnostics, monitoring and therapeutic guidance. However, current molecular diagnostic and sequencing methods are not well suited to the routine assessment of epigenetic heterogeneity in difficult samples such as liquid biopsies that contain intrinsically low fractional concentrations of circulating tumor DNA (ctDNA) and rare epigenetic subclonal populations. Here we report an alternative approach, deemed DREAMing (Discrimination of Rare EpiAlleles by Melt), which uses semi-limiting dilution and precise melt curve analysis to distinguish and enumerate individual copies of epiallelic species at single-CpG-site resolution in fractions as low as 0.005%, providing facile and inexpensive ultrasensitive assessment of locus-specific epigenetic heterogeneity directly from liquid biopsies. The technique is demonstrated here for the evaluation of epigenetic heterogeneity at p14(ARF) and BRCA1 gene-promoter loci in liquid biopsies obtained from patients in association with non-small cell lung cancer (NSCLC) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), respectively.

Indexed as

BiopsyDNA MethylationEpigenesis, GeneticAllelesCarcinoma, Non-Small-Cell LungCpG IslandsData Interpretation, StatisticalDNA, NeoplasmDNA PrimersEpigenomicsGenetic VariationHumansLung NeoplasmsMaleMyelodysplastic SyndromesNeoplasmsDNA, NeoplasmDNA PrimersTumor Suppressor Protein p14ARF

Identifiers

PMID26304549
PMCPMC4678844
OpenAlexW1851645990

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.