ArticleGenome biology2018
Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.
Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 130 citations in OpenAlex.
- Neoadjuvant sintilimab plus chemotherapy in EGFR-mutant NSCLC: Phase 2 trial interim results (NEOTIDE/CTONG2104).Cell reports. Medicine · 2024Trial
- A guide to understanding tumour evolution through the lens of population genetics.Nature reviews. Cancer · 2026Review
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- No evidence of immunosurveillance in mutation-hotspot-driven clonal hematopoiesis.Nature genetics · 2026Article
- CKS1B is a tumor-intrinsic factor driving CD8Science advances · 2026Article
- Spatial tumor evolution panorama of ovarian cancer.Cell reports. Medicine · 2026Article
- Overcoming impaired antigen presentation in tumor-draining lymph nodes facilitates immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Divergent accumulation patterns of SNVs and INDELs reveal negative selection in noncancerous cells.Innovation (Cambridge (Mass.)) · 2025Article
- Overcoming impaired antigen presentation in tumor draining lymph nodes facilitates immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- Genome-level selection in tumors as a universal marker of resistance to therapy.Nature communications · 2025Article
- Copy-number alterations in cell-free DNA can be transient or harbingers of clonal hematopoiesis.NPJ precision oncology · 2025Article
- Comprehensive assessment of computational methods for cancer immunoediting.Cell reports methods · 2025Article
- The Cancer Genome in the Long Reads Era.Methods in molecular biology (Clifton, N.J.) · 2025Article
- The theory of massively repeated evolution and full identifications of cancer-driving nucleotides (CDNs).eLife · 2024Article
- Article
- Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.Genome medicine · 2024Article
- Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations.Nature communications · 2024Article
- Immune evasion impacts the landscape of driver genes during cancer evolution.Genome biology · 2024Article
- Frequency-dependent selection of neoantigens fosters tumor immune escape and predicts immunotherapy response.Communications biology · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 6 institutions in 4 countries.
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Abstract
backgroundNatural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic.
resultsHere, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly conserved are those that play fundamental cellular roles such as protein synthesis, glucose metabolism, and molecular transport. Intriguingly, we observe strong signals of selection in the immunopeptidome and proteins controlling peptide exposition, highlighting the importance of immune surveillance evasion. Additionally, tumor type-specific immune activity correlates with the strength of negative selection on human epitopes.
conclusionsIn summary, our results show that negative selection is a hallmark of cell essentiality and immune response in cancer. The functional domains identified could be exploited therapeutically, ultimately allowing for the development of novel cancer treatments.
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