ArticleGastroenterology2024
Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention.
Article in Gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 26 citations in OpenAlex.
- Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial.Nature medicine · 2026Trial
- Colonic Polyp Regression After Nous-209 Cancer Immunotherapy: A Clinical Trial Case Report.Journal of immunotherapy and precision oncology · 2026Article
- Unique circulating miRNAome signatures captured with distinct molecular states in Lynch syndrome and sporadic colorectal cancer.Molecular oncology · 2026Article
- Exercise-associated epigenetic remodeling and TCR repertoire dynamics in Lynch syndrome carriers.iScience · 2026Article
- Mutations Targeted by Nous-209 Immunotherapy Occur Early in Lynch Syndrome Carriers' Precancer Lesions with Microsatellite Instability.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Vaccine strategies for cancer prevention in Lynch syndrome: the potential of dendritic cell-based therapy.Familial cancer · 2026Review
- Genomic analysis of T Cell receptors reveals lynch syndrome specific immune signatures.Nature communications · 2026Article
- NOUS-209 Off-the-shelf Immunotherapy Has the Potential to Hit Primary and Metachronous Colorectal and Urothelial Cancers in Lynch Syndrome.Molecular cancer therapeutics · 2026Article
- Lynch Syndrome as a Spectrum of Four Distinct Genetic Disorders: Toward Genotype-Guided Precision Management in the NGS Era.Cancers · 2026Review
- Immune interception in cancer: prioritizing vaccination in high-risk and premalignant settings.Frontiers in immunology · 2026Article
- Patterns of hypermutation shape tumorigenesis and immunotherapy response in mismatch-repair-deficient glioma.Nature genetics · 2026Article
- Mismatch Repair as a Dynamic and Clinically Actionable Vulnerability in Cancer.Cancer research · 2025Review
- Advances in Hereditary Colorectal Cancer: How Precision Medicine Is Changing the Game.Cancers · 2025Review
- Precision Prevention Studies: A Targeted Approach to Cancer Prevention.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Predictive effect and clinical diagnosis significance of exosome-related genes for nonalcoholic fatty liver disease-related hepatocellular carcinoma.Scientific reports · 2025Article
- Discovery and validation of frameshift-derived neopeptides in Lynch syndrome: paving the way for novel cancer prevention strategies.Journal for immunotherapy of cancer · 2025Article
- Distinct dysregulated pathways in sporadic and Lynch syndrome-associated colorectal cancer offer insights for targeted treatment.FEBS letters · 2025Article
- Endoplasmic Reticulum-Targeted Phototherapy Remodels the Tumor Immunopeptidome to Enhance Immunogenic Cell Death and Adaptive Anti-Tumor Immunity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- [The role of immunosurveillance and immunoediting in hereditary cancer predisposition syndromes].Magyar onkologia · 2025Review
- Inhibition of histone methyltransferase EZH2 for immune interception of colorectal cancer in Lynch syndrome.JCI insight · 2025Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsLynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers.
methodsWe generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays.
resultsMutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8
conclusionsShared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers.
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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.