ArticleGenes & development2016
Mutation of cancer driver MLL2 results in transcription stress and genome instability.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 129 citations in OpenAlex.
- Molecular and immunohistochemical characterization of cribriform-morular thyroid carcinoma: insights into its origin and therapeutic targets.Journal of endocrinological investigation · 2026Article
- Rpd3L regulates transcription-replication conflict via H3K4 methylation-dependent and -independent chromatin mechanisms.Science advances · 2026Article
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- Next generation sequencing identifies novel gene alterations with potential prognostic relevance in pediatric cancer: a single-center study.The oncologist · 2026Article
- Subtyping atypical eosinophilic renal cell tumours through integrated morphological, immunohistochemical, and mutational characters.BMC cancer · 2026Article
- Adjuvant FOLFIRINOX versus S-1 monotherapy for resected PDAC: retrospective real-world data.Therapeutic advances in medical oncology · 2026Article
- Advances in Personalized Treatment and Prognostic Factors of Follicular Lymphoma.Current treatment options in oncology · 2025Review
- Mapping in silico genetic networks of the KMT2D tumour suppressor gene to uncover novel functional associations and cancer cell vulnerabilities.Genome medicine · 2024Article
- Rapid Progression of Malignant Peritoneal Mesothelioma Mimicking a Postoperative Complication in a Young Woman: A Case Report.The American journal of case reports · 2024Article
- Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression.Genome biology · 2024Article
- Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts.Nucleic acids research · 2024Article
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- Somatic mutations of MLL4/COMPASS induce cytoplasmic localization providing molecular insight into cancer prognosis and treatment.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The mutational pattern of homologous recombination repair genes in urothelial carcinoma and its correlation with immunotherapeutic response.Cancer medicine · 2023Article
- Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma.Journal of biomedical science · 2023Review
- KMT2D Deficiency Promotes Myeloid Leukemias which Is Vulnerable to Ribosome Biogenesis Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Association of KMT2C/D loss-of-function variants with response to immune checkpoint blockades in colorectal cancer.Cancer science · 2023Article
- Article
- The Somatic Mutational Landscape of Mismatch Repair Deficient Prostate Cancer.Journal of clinical medicine · 2023Article
- Next-generation sequencing in dermatology.Frontiers in medicine · 2023Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Genome instability is a recurring feature of tumorigenesis. Mutation in MLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear. Here, we present evidence that MLL2 mutation results in genome instability. Mouse cells in which MLL2 gene deletion can be induced display elevated levels of sister chromatid exchange, gross chromosomal aberrations, 53BP1 foci, and micronuclei. Human MLL2 knockout cells are characterized by genome instability as well. Interestingly, MLL2 interacts with RNA polymerase II (RNAPII) and RECQL5, and, although MLL2 mutated cells have normal overall H3K4me levels in genes, nucleosomes in the immediate vicinity of RNAPII are hypomethylated. Importantly, MLL2 mutated cells display signs of substantial transcription stress, and the most affected genes overlap with early replicating fragile sites, show elevated levels of γH2AX, and suffer frequent mutation. The requirement for MLL2 in the maintenance of genome stability in genes helps explain its widespread role in cancer and points to transcription stress as a strong driver in tumorigenesis.
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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.