ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2017
Small Cell Lung Cancer Exhibits Frequent Inactivating Mutations in the Histone Methyltransferase KMT2D/MLL2: CALGB 151111 (Alliance).
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- A multiplexed in vivo approach to identify driver genes in small cell lung cancer.Cell reports · 2023Pooled it
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Review
- Radiographically occult bone marrow metastasis in relapsed small cell lung cancer presenting with rapidly progressive thrombocytopenia: a case report.Frontiers in oncology · 2026Article
- EP300 compromises antitumor immunity by increasing SOCS1 expression.Journal for immunotherapy of cancer · 2025Article
- Comprehensive Analysis of the Value of Dynamic Changes in Circulating Tumor DNA in Small Cell Lung Cancer.JCO precision oncology · 2025Article
- What Is On the Horizon for the Diagnosis and Treatment of SCLC and Large Cell Neuroendocrine Cancer?JTO clinical and research reports · 2025Review
- Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Molecular cancer therapeutics · 2025Review
- Advancing therapeutics in small-cell lung cancer.Nature cancer · 2025Review
- In vivo functional screens revealScience advances · 2025Article
- Proteogenomic Characterization of High-Grade Lung Neuroendocrine Carcinoma Deciphers Molecular Diversity and Potential Biomarkers of Different Histological Subtypes in Chinese Population.Research (Washington, D.C.) · 2025Article
- Genomic Profiling of Extensive Stage Small-Cell Lung Cancer Patients Identifies Molecular Factors Associated with Survival.Lung Cancer (Auckland, N.Z.) · 2025Article
- Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets.MedComm · 2024Review
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- SomaticJournal of thoracic disease · 2024Article
- Molecular phenotyping of small cell lung cancer using targeted cfDNA profiling of transcriptional regulatory regions.Science advances · 2024Article
- Comparison of mutation landscapes of pretreatment versus recurrent squamous cell carcinoma of the oral cavity: The possible mechanism of resistance to standard treatment.Cancer reports (Hoboken, N.J.) · 2024Article
- Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer.Molecular cancer · 2024Review
- Review
- KDM6A epigenetically regulates subtype plasticity in small cell lung cancer.Nature cell biology · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
introductionSCLC is a lethal neuroendocrine tumor type that is highly prone to metastasis. There is an urgency to understand the mutated genes that promote SCLC, as there are no approved targeted therapies yet available. SCLC is rarely resected, limiting the number of samples available for genomic analyses of somatic mutations.
methodsTo identify potential driver mutations in human SCLC we sequenced the whole exomes of 18 primary SCLCs and seven cell lines along with matched normal controls. We extended these data by resequencing a panel of genes across 40 primary SCLCs and 48 cell lines.
resultsWe report frequent mutations in the lysine methyltransferase 2D gene (KMT2D) (also known as MLL2), a key regulator of transcriptional enhancer function. KMT2D exhibited truncating nonsense/frameshift/splice site mutations in 8% of SCLC tumors and 17% of SCLC cell lines. We found that KMT2D mutation in human SCLC cell lines was associated with reduced lysine methyltransferase 2D protein levels and reduced monomethylation of histone H3 lysine 4, a mark associated with transcriptional enhancers. We also found mutations in other genes associated with transcriptional enhancer control, including CREB binding protein gene (CREBBP), E1A binding protein p300 gene (EP300), and chromodomain helicase DNA binding protein 7 gene (CHD7), and we report mutations in additional chromatin remodeling genes such as polybromo 1 gene (PBRM1).
conclusionsThese data indicate that KMT2D is one of the major mutated genes in SCLC, and they point to perturbation of transcriptional enhancer control as potentially contributing to SCLC.
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Registered trials
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