title: Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in the DICER1 gene and additional manifestations of the DICER1 syndrome.
abstract: Germline mutations in the DICER1 gene are associated with an inherited cancer predisposition syndrome also known as the DICER1-syndrome, which is implicated in a broad range of tumors including pleuropulmonary blastoma, ovarian Sertoli-Leydig cell tumors, ciliary body medulloepithelioma (CBME), pituitary blastoma, embryonal rhabdomyosarcoma (eRMS), anaplastic renal sarcoma as well as ocular, sinonasal tumors ovarian sex-cord tumors, thyroid neoplasia and cystic nephroma. This study describes a novel, heterozygous frameshift DICER1 mutation in a patient, who is affected by different tumors of the DICER1-syndrome, including eRMS, CBME and suspected pleuropulmonary blastoma type I. By whole-exome sequencing of germline material using peripheral blood-derived DNA, we identified a single base pair duplication within the DICER1 gene (c.3405 dupA) that leads to a frameshift and results in a premature stop in exon 21 (p.Gly1136Arg). The metachronous occurrence of two unrelated tumor entities (eRMS and CBME) in a very young child within a short timeframe should have raised the suspicion of an underlying cancer susceptibility syndrome and should be prompt tested for DICER1.
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Fremerey
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Balzer
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
authors.forename: Triantafyllia
authors.initials: T
authors.lastname: Brozou
authors.affiliation: Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schaper
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Borkhardt
authors.affiliation: Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany. Michaela.Kuhlen@med.uni-duesseldorf.de.
authors.forename: Michaela
authors.identifier: 0000-0003-4577-0503
authors.initials: M
authors.lastname: Kuhlen
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics; D002648:Child; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D018242:Neuroectodermal Tumors, Primitive / Q000235:genetics; D018202:Pulmonary Blastoma / Q000235:genetics; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics*; D043244:Ribonuclease III / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: DICER1 germline mutation; DICER1-syndrome; Embryonal rhabdomyosarcoma; Focal nodular hyperplasia; Frameshift; Medulloepithelioma; Pleuropulmonary blastoma; Renal cysts