The prevalence of germline DICER1 pathogenic variation in cancer populations.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30672147", "kind": "science-record", "revision": 3, "content_hash": "sha256:0316d651373d910721dc6db03da121081e77d052a8fcf36aad06e072cfaa87b3", "created_at": "2026-11-01T15:40:41Z", "updated_at": "2026-11-01T18:50:21Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The prevalence of germline DICER1 pathogenic variation in cancer populations.", "doi": "10.1002/mgg3.555", "pmid": "30672147", "authors": ["Jung Kim", "Kris Ann P Schultz", "Dana Ashley Hill", "Douglas R Stewart"], "journal": "Molecular genetics & genomic medicine", "year": 2019, "abstract": "BACKGROUND: The DICER1 syndrome is an autosomal dominant tumor-predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense variation in \"hotspot\" codons in the RNaseIIIb domain (E1705, D1709, G1809, D1810, E1813) is observed in DICER1-associated tumors. Previously, we found the prevalence of germline pathogenic DICER1 variation in the general population is 1:10,600. In this study, we investigated the prevalence of pathogenic DICER1 germline variation in The Cancer Genome Atlas (TCGA; 32 adult cancer types; 9,173 exomes) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET; two pediatric cancer types; 175 exomes) cohorts.\nMETHODS: All datasets were annotated and binned into four categories: pathogenic, likely pathogenic, variant of unknown significance, or likely benign.\nRESULTS: The prevalence of DICER1 pathogenic variants was 1:4,600 in TCGA. A single participant with a uterine corpus endometrial carcinoma harbored two pathogenic germline DICER1 (hotspot and splice-donor) variants, and a single participant with a rectal adenocarcinoma harbored a germline DICER1 stop-gained variant. In the smaller TARGET dataset, we observed no pathogenic germline variants.\nCONCLUSION: This is the largest comprehensive analysis of DICER1 pathogenic variation in adult and pediatric cancer populations using publicly available data. The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.", "claims": [{"id": "claim-data-access", "statement": "The data used for this analysis are available phs000218.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30672147", "locator": "sections[17] \"ACKNOWLEDGMENTS\" paragraph 2", "quote": "The data used for this analysis are available phs000218."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30672147"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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n)", "Gender", "Age at diagnosis (years)", "Race", "DICER1 germline", "DICER1 somatic", "Frequency of variant in database", "Vital status"], ["ExAC non‐TCGA", "ESP", "1,000 genomes"], ["Breast invasive carcinoma (BRCA; 966)", "Female", "43", "White", "p.Gly1824Val", "None", "None", "7.7 × 10−5", "None", "Living/disease free"], ["Bladder urothelial carcinoma (BLCA; 394)", "Female", "82", "Asian", "p.Ser1160Tyr", "None", "4.71 × 10−5", "None", "None", "Living/disease free Brother colon cancer"], ["Male", "70", "White", "p.Ala1578Thr", "None", "None", "None", "None", "Living/recurred/progressed Prior cancer history/mother breast cancer"], ["Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC; 300)", "Female", "62", "White", "p.Leu1469Pro", "None", "1.89 × 10−5", "None", "3.99x10−4", "Living/disease free"], ["Female", "72", "Asian", "p.Ser1160Tyr", "None", "4.71 × 10−5", "None", "None", "Living/disease free"], ["Lymphoid neoplasm diffuse large B‐cell lymphoma (DLBC; 44)", "Male", "36", "White", "p.Ile528Thr", "None", "1.88 × 10−5", "2.0 × 10−4", "None", "Living/disease free"], ["Thyroid carcinoma (THCA; 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