Evidence map›Paper›PMID 25860294›Full record

ArticleBlood cancer journal2015

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development.

E N Smith, E M Ghia, C M DeBoever, L Z Rassenti, K Jepsen, K-A Yoon, H Matsui, S Rozenzhak, H Alakus, P J Shepard and 13 more

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

Article in Blood cancer journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Clonal dynamics in chronic lymphocytic leukemia.Hematology. American Society of Hematology. Education Program · 2019
    Review
  5. Article
  6. Article
  7. Article
  8. Methylation alteration ofOncotarget · 2019
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. 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

23 authors at 4 institutions in 1 country.

E N Smith1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
E M Ghia1] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [2] Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
C M DeBoeverBioinformatics and Systems Biology Program, University of California at San Diego, La Jolla, CA, USA.
L Z Rassenti1] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [2] Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
K JepsenInstitute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
K-A YoonPediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA.
H Matsui1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
S Rozenzhak1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
H Alakus1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
P J Shepard1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
Y Dai1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
M KhosroheidariInstitute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
M BinaDepartment of Chemistry, Purdue University, West Lafayette, IN, USA.
K L GundersonIllumina, Inc., 5200 Illumina Way, San Diego, CA, USA.
K MesserMoores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
L Muthuswamy1] Ontario Institute for Cancer Research, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
T J Hudson1] Ontario Institute for Cancer Research, Toronto, Ontario, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
O Harismendy1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
C L Barrett1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA.
C H M Jamieson1] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [2] Department of Medicine, University of California at San Diego, La Jolla, CA, USA [3] Stem Cell Program, University of California San Diego, La Jolla, CA, USA.
D A Carson1] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [2] Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
T J Kipps1] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [2] Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
K A Frazer1] Pediatrics and Rady's Children's Hospital, University of California at San Diego, La Jolla, CA, USA [2] Moores Cancer Center, University of California at San Diego, La Jolla, CA, USA [3] Bioinformatics and Systems Biology Program, University of California at San Diego, La Jolla, CA, USA [4] Institute for Genomic Medicine, University of California at San Diego, La Jolla, CA, USA.
University of California, San Diego · USIllumina (United States) · USMoores Cancer CenterPurdue University West Lafayette · US

Funding

VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9M
Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
UCSD Cancer Center Training Program in Drug DevelopmentT32CA121938 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Bouvet, Dwayne G. Stupack · 2006 to 2026
$10.3M
Biomarkers of Disease Progression in CLLR21CA152613 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FRAZER, KELLY A · 2010 to 2011
$367k
Canadian Institutes of Health Research CSC-105367NCATS NIH HHS UL1 TR000100NCATS NIH HHS UL1TR000100NCI NIH HHS 1R21CA152613NCI NIH HHS P01 CA081534NCI NIH HHS P30 CA023100NCI NIH HHS P30CA023100NCI NIH HHS R21 CA152613NCI NIH HHS T32 CA121938NCI NIH HHS T32CA121938
6 · The paper itself

Abstract

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells.

Indexed as

Epigenesis, GeneticClonal EvolutionCpG IslandsDisease ProgressionDNA MethylationHumansLeukemia, Lymphocytic, Chronic, B-CellMutationPolycomb-Group ProteinsPolycomb-Group Proteins

Identifiers

PMID25860294
PMCPMC4450323
OpenAlexW2017202925

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.