Evidence map›Paper›PMID 31171663›Full record

ArticleScience (New York, N.Y.)2019

RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues.

Keren Yizhak, François Aguet, Jaegil Kim, Julian M Hess, Kirsten Kübler, Jonna Grimsby, Ruslana Frazer, Hailei Zhang, Nicholas J Haradhvala, Daniel Rosebrock and 10 more

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

Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 294 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
294citing papers in PubMed, 1 pooled it
27.2field-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

294 citing papers in PubMed, 1 synthesis or guideline pooled it, 504 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa.medRxiv : the preprint server for health sciences · 2026
    Article
  6. Article
  7. Article
  8. The aging genome exhibits organized vulnerability to somatic mutations.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026
    Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 2 countries.

Keren YizhakBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-4454-796X
François AguetBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-9414-300X
Jaegil KimBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Julian M HessBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-1387-4009
Kirsten KüblerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jonna GrimsbyBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-2304-7656
Ruslana FrazerBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Hailei ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas J HaradhvalaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Daniel RosebrockBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Dimitri LivitzBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Xiao LiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-6283-6511
Eila Arich-LandkofBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-4202-9525
Noam ShoreshBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-5482-5046
Chip StewartBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-2245-9552
Ayellet V SegrèBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-6806-5845
Philip A BrantonBiorepositories and Biospecimen Research Branch, Cancer Diagnosis Program, National Cancer Institute, Bethesda, MD, USA.ORCID 0000-0002-0898-9605
Paz PolakOncological Sciences, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.ORCID 0000-0002-2153-4488
Kristin G ArdlieBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-4272-6283
Gad GetzBroad Institute of MIT and Harvard, Cambridge, MA, USA. gadgetz@broadinstitute.org.ORCID 0000-0002-0936-0753
Broad Institute · USMount Sinai Hospital · USSpecim (Finland) · FI

Funding

MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
NHLBI NIH HHS HHSN268201000029CNIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants, demonstrating that macroscopic clones can be found in many normal tissues. We found that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, which suggests that environmental factors can promote somatic mosaicism. Mutation burden was associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over both time and number of cell divisions. Finally, normal tissues were found to harbor mutations in known cancer genes and hotspots. This study provides a broad view of macroscopic clonal expansion in human tissues, thus serving as a foundation for associating clonal expansion with environmental factors, aging, and risk of disease.

Indexed as

Clone CellsDNA Mutational AnalysisFemaleHumansMaleNeoplasmsOrgan SpecificitySequence Analysis, RNA

Identifiers

PMID31171663
PMCPMC7350423
OpenAlexW2948371032

What OpenQuestion holds

Textmetadata
LicenceTDM
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.