Trial reportThe Journal of clinical investigation2020
DGCR8 microprocessor defect characterizes familial multinodular goiter with schwannomatosis.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- From bench to bedside: the evolving role of iodine in thyroid cancer management.Nature reviews. Endocrinology · 2026Review
- Canonical microRNA loss drives tumor development, implicating therapeutic efficacy of enoxacin in angiosarcoma.RNA (New York, N.Y.) · 2026Article
- mirtronDB 2.0: enhanced database with novel mirtron discoveries.Bioinformatics (Oxford, England) · 2026Article
- Tracing the molecular route to progression in miRNA-biogenesis-defective thyroid lesions.JCI insight · 2026Article
- Schwannomatosis tumor modeling: progress and prospects for translational research.Journal of biological engineering · 2026Review
- DGCR8 regulates multiple processes of transcription coupled nucleotide excision repair.Scientific reports · 2026Article
- DICER1 and DGCR8 in thyroid tumorigenesis: miRNA biogenesis and histopathologic diversity.European thyroid journal · 2025Review
- Novel susceptibility genes for non-NF2-/LZTR1-/SMARCB1-related hereditary schwannomatosis.Familial cancer · 2025Review
- Molecular pathogenesis of the schwannomatosis genes and genetic testing strategies.Familial cancer · 2025Review
- Hybrid neurofibroma/schwannoma in schwannomatosis-a diagnostically challenging benign peripheral nerve sheath tumour.Familial cancer · 2025Review
- Towards a WHO classification of genetic tumour syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- History and clinical epidemiology of NF2-related schwannomatosis.Familial cancer · 2025Review
- Progression of Follicular Thyroid Carcinomas to Anaplastic Thyroid Carcinomas: Molecular and Clinicopathologic Characteristics with Comparison to Papillary Thyroid Carcinoma-Derived Anaplastic Thyroid Carcinomas.Endocrine pathology · 2025Article
- SMARCB1-related schwannomatosis and other SMARCB1-associated phenotypes: clinical spectrum and molecular pathogenesis.Familial cancer · 2025Review
- Canonical microRNA loss drives tumor development implicating therapeutic efficacy of enoxacin in angiosarcoma.bioRxiv : the preprint server for biology · 2025Article
- Assessing Microprocessor complex mutations with a Microsensor system.RNA (New York, N.Y.) · 2025Article
- Germline Pathogenic DROSHA Variants Are Linked to Pineoblastoma and Wilms Tumor Predisposition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Update on Cancer and Central Nervous System Tumor Surveillance in Pediatric NF2-, SMARCB1-, and LZTR1-Related Schwannomatosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Fine Regulation of MicroRNAs in Gene Regulatory Networks and Pathophysiology.International journal of molecular sciences · 2025Review
- Nodule-Specific NRF2-Targeted Upregulation in Patients With KEAP1 Mutations and Familial Nontoxic Multinodular Goiter.The Journal of clinical endocrinology and metabolism · 2025Article
Corrections and comments
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Authors and funding
32 authors at 10 institutions in 3 countries.
Funding
Abstract
BACKGROUNDDICER1 is the only miRNA biogenesis component associated with an inherited tumor syndrome, featuring multinodular goiter (MNG) and rare pediatric-onset lesions. Other susceptibility genes for familial forms of MNG likely exist.METHODSWhole-exome sequencing of a kindred with early-onset MNG and schwannomatosis was followed by investigation of germline pathogenic variants that fully segregated with the disease. Genome-wide analyses were performed on 13 tissue samples from familial and nonfamilial DGCR8-E518K-positive tumors, including MNG, schwannomas, papillary thyroid cancers (PTCs), and Wilms tumors. miRNA profiles of 4 tissue types were compared, and sequencing of miRNA, pre-miRNA, and mRNA was performed in a subset of 9 schwannomas, 4 of which harbor DGCR8-E518K.RESULTSWe identified c.1552G>A;p.E518K in DGCR8, a microprocessor component located in 22q, in the kindred. The variant identified is a somatic hotspot in Wilms tumors and has been identified in 2 PTCs. Copy number loss of chromosome 22q, leading to loss of heterozygosity at the DGCR8 locus, was found in all 13 samples harboring c.1552G>A;p.E518K. miRNA profiling of PTCs, MNG, schwannomas, and Wilms tumors revealed a common profile among E518K hemizygous tumors. In vitro cleavage demonstrated improper processing of pre-miRNA by DGCR8-E518K. MicroRNA and RNA profiling show that this variant disrupts precursor microRNA production, impacting populations of canonical microRNAs and mirtrons.CONCLUSIONWe identified DGCR8 as the cause of an unreported autosomal dominant mendelian tumor susceptibility syndrome: familial multinodular goiter with schwannomatosis.FUNDINGCanadian Institutes of Health Research, Compute Canada, Alex's Lemonade Stand Foundation, the Mia Neri Foundation for Childhood Cancer, Cassa di Sovvenzioni e Risparmio fra il Personale della Banca d'Italia, and the KinderKrebsInitiative Buchholz/Holm-Seppensen.
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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.