ArticleGenome medicine2019
Evolving neoantigen profiles in colorectal cancers with DNA repair defects.
Article in Genome medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Temozolomide Treatment Alters Mismatch Repair and Boosts Mutational Burden in Tumor and Blood of Colorectal Cancer Patients.Cancer discovery · 2022Trial
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Tissue and cellular spatiotemporal dynamics in colon aging.Nature biotechnology · 2026Article
- DNA demethylation triggers cell free DNA release in colorectal cancer cells.Genome medicine · 2024Article
- The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors.NPJ precision oncology · 2024Review
- Mutational Signatures in Colorectal Cancer: Translational Insights, Clinical Applications, and Limitations.Cancers · 2024Review
- A pan-cancer interrogation of intronic polyadenylation and its association with cancer characteristics.Briefings in bioinformatics · 2024Article
- Mutational signatures of colorectal cancers according to distinct computational workflows.Briefings in bioinformatics · 2024Article
- Unravelling immune microenvironment features underlying tumor progression in the single-cell era.Cancer cell international · 2024Review
- Recurrent mutations in tumor suppressorScience advances · 2024Article
- Dendritic cell-targeted therapy expands CD8 T cell responses to bona-fide neoantigens in lung tumors.Nature communications · 2024Article
- Advances in DNA damage response inhibitors in colorectal cancer therapy.Acta biochimica et biophysica Sinica · 2024Review
- Non-canonical antigens are the largest fraction of peptides presented by MHC class I in mismatch repair deficient murine colorectal cancer.Genome medicine · 2024Article
- Genomic instability as a driver and suppressor of anti-tumor immunity.Frontiers in immunology · 2024Review
- In Silico: Predicting Intrinsic Features of HLA Class-I Restricted Neoantigens.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Neo-Antigen-Reactive T Cells Immunotherapy for Colorectal Cancer: A More Personalized Cancer Therapy Approach.Global challenges (Hoboken, NJ) · 2023Review
- Cellular and molecular features related to exceptional therapy response and extreme long-term survival in glioblastoma.Cancer medicine · 2023Review
- Review
- Chronic hypoxia is associated with transcriptomic reprogramming and increased genomic instability in cancer cells.Frontiers in cell and developmental biology · 2023Article
- Colorectal Cancer Immunotherapy: State of the Art and Future Directions.Gastro hep advances · 2023Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeoantigens that arise as a consequence of tumor-specific mutations can be recognized by T lymphocytes leading to effective immune surveillance. In colorectal cancer (CRC) and other tumor types, a high number of neoantigens is associated with patient response to immune therapies. The molecular processes governing the generation of neoantigens and their turnover in cancer cells are poorly understood. We exploited CRC as a model system to understand how alterations in DNA repair pathways modulate neoantigen profiles over time.
methodsWe performed whole exome sequencing (WES) and RNA sequencing (RNAseq) in CRC cell lines, in vitro and in vivo, and in CRC patient-derived xenografts (PDXs) to track longitudinally genomic profiles, clonal evolution, mutational signatures, and predicted neoantigens.
resultsThe majority of CRC models showed remarkably stable mutational and neoantigen profiles; however, those carrying defects in DNA repair genes continuously diversified. Rapidly evolving and evolutionary stable CRCs displayed characteristic genomic signatures and transcriptional profiles. Downregulation of molecules implicated in antigen presentation occurred selectively in highly mutated and rapidly evolving CRC.
conclusionsThese results indicate that CRCs carrying alterations in DNA repair pathways display dynamic neoantigen patterns that fluctuate over time. We define CRC subsets characterized by slow and fast evolvability and link this phenotype to downregulation of antigen-presenting cellular mechanisms. Longitudinal monitoring of the neoantigen landscape could be relevant in the context of precision medicine.
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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.