ArticleScience advances2023
Gain-of-function mutations in the catalytic domain of
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- The safety and efficacy of binimetinib for lung cancer: a systematic review.BMC pulmonary medicine · 2024Pooled it
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- DOT1L promotes immune evasion in lung adenocarcinoma through H3K79me2-mediated epigenetic activation of immune checkpoints.Frontiers in immunology · 2026Article
- DOT1L as a Therapeutic Target: Insights into Epigenetic Regulation and Cancer Treatment.Biomolecules & therapeutics · 2025Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Cancer-associated loss-of-function mutations in KCNQ1 enhance Wnt/β-catenin signalling disrupting epithelial homeostasis.Oncogene · 2025Article
- Transcription-Replication Conflicts: Unlocking New Frontiers in Cancer.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- DOT1L Mediates Stem Cell Maintenance and Represents a Therapeutic Vulnerability in Cancer.Cancer research · 2025Review
- Effect of the CSFV NS5A protein on key proteins in the MAPK and PI3K-mTOR signaling pathways in porcine macrophages.Frontiers in microbiology · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Discovery of first-in-class DOT1L inhibitors against the R231Q gain-of-function mutation in the catalytic domain with therapeutic potential of lung cancer.Acta pharmaceutica Sinica. B · 2024Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is a lethal malignancy lacking effective therapies. Emerging evidence suggests that epigenetic enzyme mutations are closely related to the malignant phenotype of lung cancer. Here, we identified a series of gain-of-function mutations in the histone methyltransferase DOT1L. The strongest of them is R231Q, located in the catalytic DOT domain. R231Q can enhance the substrate binding ability of DOT1L. Moreover, R231Q promotes cell growth and drug resistance of lung cancer cells in vitro and in vivo. Mechanistic studies also revealed that the R231Q mutant specifically activates the MAPK/ERK signaling pathway by enriching H3K79me2 on the
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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.