Evidence map›Paper›PMID 23297126›Full record

ArticleBlood2013

Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma.

Michael R Green, Andrew J Gentles, Ramesh V Nair, Jonathan M Irish, Shingo Kihira, Chih Long Liu, Itai Kela, Erik S Hopmans, June H Myklebust, Hanlee Ji and 3 more

Abstract readComparative Study
In one paragraph

Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed, 2 pooled it
23.1field-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

170 citing papers in PubMed, 2 syntheses or guidelines pooled it, 319 citations in OpenAlex.

  1. Guideline
  2. A genetic profiling guideline to support diagnosis and clinical management of lymphomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Guideline
  3. Trial
  4. Blood · 2018
    Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Heterogeneity in primary gastrointestinal DLBCL: from clinical management to molecular mechanisms and treatment strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  10. Article
  11. CD20-Targeted α-Radionuclides Synergize with Immune Checkpoint Inhibition to Treat Murine Lymphoma.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Missense Mutations in the KAT Domain ofInternational journal of molecular sciences · 2025
    Article
  17. Article
  18. Review
  19. Article
  20. Article

110 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 2 countries.

Michael R GreenDivision of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Andrew J Gentles
Ramesh V Nair
Jonathan M Irish
Shingo Kihira
Chih Long Liu
Itai Kela
Erik S Hopmans
June H Myklebust
Hanlee Ji
Sylvia K Plevritis
Ronald Levy
Ash A Alizadeh
Center for Systems Biology · USNew York Genome Center · USOslo University Hospital · NOVanderbilt University · US

Funding

TRIGGERING CELL DEATH IN B CELL LYMPHOMAP01CA034233 · NCI · STANFORD UNIVERSITY · PI FELSHER, DEAN W · 1985 to 2010
$19.5M
MODELING THE ROLE OF PROGRESSION IN FOLLICULAR LYMPHOMAU54CA149145 · NCI · STANFORD UNIVERSITY · PI PLEVRITIS, SYLVIA KATINA · 2010 to 2014
$12.1M
Genetic Basis of Signaling Heterogeneity in Human Follicular LymphomaR01CA151748 · NCI · STANFORD UNIVERSITY · PI LEVY, RONALD · 2011 to 2015
$2.4M
Targeting the B Cell Receptor Signaling Network in LymphomaR00CA143231 · NCI · VANDERBILT UNIVERSITY · PI IRISH, JONATHAN MICHAEL · 2012 to 2014
$715k
Targeting the B Cell Receptor Signaling Network in LymphomaK99CA143231 · NCI · STANFORD UNIVERSITY · PI IRISH, JONATHAN MICHAEL · 2009 to 2009
$136k
NCI NIH HHS K99 CA143231NCI NIH HHS P01 CA034233NCI NIH HHS R00 CA143231NCI NIH HHS R01 CA151748NCI NIH HHS U54 CA149145
6 · The paper itself

Abstract

Follicular lymphoma (FL) is currently incurable using conventional chemotherapy or immunotherapy regimes, compelling new strategies. Advances in high-throughput sequencing technologies that can reveal oncogenic pathways have stimulated interest in tailoring therapies toward actionable somatic mutations. However, for mutation-directed therapies to be most effective, the mutations must be uniformly present in evolved tumor cells as well as in the self-renewing tumor-cell precursors. Here, we show striking intratumoral clonal diversity within FL tumors in the representation of mutations in the majority of genes as revealed by whole exome sequencing of subpopulations. This diversity captures a clonal hierarchy, resolved using immunoglobulin somatic mutations and IGH-BCL2 translocations as a frame of reference and by comparing diagnosis and relapse tumor pairs, allowing us to distinguish early versus late genetic eventsduring lymphomagenesis. We provide evidence that IGH-BCL2 translocations and CREBBP mutations are early events, whereas MLL2 and TNFRSF14 mutations probably represent late events during disease evolution. These observations provide insight into which of the genetic lesions represent suitable candidates for targeted therapies.

Indexed as

Clonal EvolutionClone CellsDisease ProgressionDNA, NeoplasmExomeGene FrequencyGenome, HumanHigh-Throughput Nucleotide SequencingHumansImmunophenotypingLymphoma, FollicularMutationMutation RatePolymerase Chain ReactionRecurrenceDNA, Neoplasm

Identifiers

PMID23297126
PMCPMC3587323
OpenAlexW1966524014

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.