ArticleGut2019
Evolutionary history of human colitis-associated colorectal cancer.
Article in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
What it found
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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.
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Who cites it
94 citing papers in PubMed, 157 citations in OpenAlex.
- Colitis-associated colorectal carcinogenesis: molecular mechanisms and therapeutic potential.Molecular biomedicine · 2026Review
- Paired mutation calling and spatial transcriptomics identify cellular neighborhoods associated with the neoplastic outcome of mouse colitis.Nature genetics · 2026Article
- 5-FU chemotherapy induces functional CD7Science China. Life sciences · 2026Article
- Beyond the Stomach: Exploring the Role ofExpert reviews in molecular medicine · 2026Review
- Pathophysiology of colitis-associated colorectal cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
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- Single-cell and spatial profiling in cancer biology and clinical oncology.Nature cancer · 2026Review
- Negative Selection Maintains Grossly Altered but Broadly Stable Karyotypes in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- Dendritic cell-liposome conjugates reverse immunosuppressive tumor microenvironment for inhibiting colitis-associated colorectal cancer.Acta pharmacologica Sinica · 2026Article
- The Role of Prostaglandins as Major Inflammatory Mediators in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Sessile Serrated Lesions in Inflammatory Bowel Disease: Hidden Players in Colitis-Associated Colorectal Cancer?Journal of clinical medicine · 2025Review
- Nutrition, Environment, and Genetics in Colorectal Cancer. Epigenetics and Possible Future Perspective.Current nutrition reports · 2025Review
- The intervention of NLRP3 inflammasome inhibitor: oridonin against azoxymethane and dextran sulfate sodium-induced colitis-associated colorectal cancer in male BALB/c mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Dehydrodiisoeugenol targets NOD2 exerting dual effects against colitis and colorectal cancer: a double-edged sword.Molecular medicine (Cambridge, Mass.) · 2025Article
- E3 ubiquitin ligase RNF128 attenuates colitis and colorectal tumorigenesis by triggering the degradation of IL-6 receptors.Journal of advanced research · 2025Article
- Construction and validation of a prognostic model for glioma: an analysis based on mismatch repair-related genes and their correlation with clinicopathological features.Translational cancer research · 2025Article
- Huangqin decoction inhibits colorectal inflammatory cancer transformation by improving gut microbiome-mediated metabolic dysfunction.Journal of pharmaceutical analysis · 2025Article
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34 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
26 authors at 8 institutions in 1 country.
Funding
Abstract
objectiveIBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multiregion sequencing.
designExome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.
results10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated 'catastrophic' CNA increase.
conclusionsEvolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection.
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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.