ArticleNature2016
Tissue-specific mutation accumulation in human adult stem cells during life.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05419531 (Measuring the Incidence of Colorectal Cancer in Young Endurance Athletes), which is not on this map. Cited by 588 papers.
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.
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.
Measuring the Incidence of Colorectal Cancer in Young Endurance Athletes
Who cites it
588 citing papers in PubMed, 969 citations in OpenAlex.
- Comprehensive Genomic Analysis of Normal and Cancer Cells Elucidates the Elevated Mutational Burden in Cancer.Cancer research · 2026Article
- Article
- Identification of Novel Transcriptional Alleles in Primary Prostate Cancer Cells and Cancer Stem Cells by Bulk RNA-Seq and Single-Cell RNA-Seq Analyses.Biomolecules · 2026Article
- Gastroenteropancreatic Neuroendocrine Neoplasms: Clinical and Translational Perspectives.JMA journal · 2026Review
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- The Evolution of Polyclonal Competition in Aging Hematopoiesis.Cancer discovery · 2026Article
- Integrated Multiomic Profiling Enhances Risk Stratification and Prognostication in Canine Osteosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Human PMS1-dependent non-canonical mismatch repair engages with MBD4 to repair methylated CpG deamination.Nucleic acids research · 2026Article
- Adaptive oncogenesis of β-catenin emerges from declining liver tissue integrity.Nature communications · 2026Article
- Stem cells as an essential mediator of the exercise-tumorigenesis link.Nature reviews. Cancer · 2026Review
- Methylation of theOncology letters · 2026Article
- Somatic mutations and genome mosaicism in aging and disease.Experimental & molecular medicine · 2026Review
- Advancing Human Placental Modeling Through Stem-Cell-Derived Trophoblast Organoids and Reprogramming Innovations.Biomedicines · 2026Review
- Patient-derived organoids for precision oncology in colorectal cancer: from tumor modeling to clinical translation.Molecular cancer · 2026Review
- Lineage tracing from cellular heritage to disease destiny.Nature genetics · 2026Review
- Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.Annals of translational medicine · 2026Review
- Clonal evolution and mutational trajectories of metastatic colorectal cancer shaped by anticancer therapies.Nature communications · 2026Article
- Charting single-cell lineages with synthetic and natural barcodes.Nature reviews. Genetics · 2026Review
- Spatial transcriptomics defines IM-crypt as a premalignant niche with bidirectional divergence in early gastric carcinogenesis.Communications biology · 2026Article
- Clonal hematopoiesis and its progression to myeloid neoplasms: insights into risk, biology, and therapeutic strategies.Haematologica · 2026Review
528 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 6 institutions in 3 countries.
Funding
Abstract
The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.