Skip to main content
Erschienen in: Familial Cancer 3/2017

28.11.2016 | Short Communication

Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in the DICER1 gene and additional manifestations of the DICER1 syndrome

verfasst von: Julia Fremerey, Stefan Balzer, Triantafyllia Brozou, Joerg Schaper, Arndt Borkhardt, Michaela Kuhlen

Erschienen in: Familial Cancer | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Brenneman M, Field A, Yang J, Williams G, Doros L, Rossi C et al (2015) Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model. F1000Research 4:214. doi:10.12688/f1000research.6746.1 PubMedPubMedCentral Brenneman M, Field A, Yang J, Williams G, Doros L, Rossi C et al (2015) Temporal order of RNase IIIb and loss-of-function mutations during development determines phenotype in DICER1 syndrome: a unique variant of the two-hit tumor suppression model. F1000Research 4:214. doi:10.​12688/​f1000research.​6746.​1 PubMedPubMedCentral
5.
Zurück zum Zitat Doros L, Yang J, Dehner L, Rossi CT, Skiver K, Jarzembowski J et al (2012) DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome. Pediatr Blood Cancer 59(3):558–560. doi:10.1002/pbc.24020 CrossRefPubMed Doros L, Yang J, Dehner L, Rossi CT, Skiver K, Jarzembowski J et al (2012) DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome. Pediatr Blood Cancer 59(3):558–560. doi:10.​1002/​pbc.​24020 CrossRefPubMed
6.
Zurück zum Zitat Priest JR, Williams GM, Manera R, Jenkinson H, Brundler MA, Davis S et al (2011) Ciliary body medulloepithelioma: four cases associated with pleuropulmonary blastoma—a report from the International Pleuropulmonary Blastoma Registry. Br J Ophthalmol 95(7):1001–1005. doi:10.1136/bjo.2010.189779 CrossRefPubMed Priest JR, Williams GM, Manera R, Jenkinson H, Brundler MA, Davis S et al (2011) Ciliary body medulloepithelioma: four cases associated with pleuropulmonary blastoma—a report from the International Pleuropulmonary Blastoma Registry. Br J Ophthalmol 95(7):1001–1005. doi:10.​1136/​bjo.​2010.​189779 CrossRefPubMed
7.
Zurück zum Zitat Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S et al (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48(4):273–278. doi:10.1136/jmg.2010.083790 CrossRefPubMed Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S et al (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48(4):273–278. doi:10.​1136/​jmg.​2010.​083790 CrossRefPubMed
8.
Zurück zum Zitat Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. doi:10.1038/gim.2015.30 CrossRefPubMedPubMedCentral Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424. doi:10.​1038/​gim.​2015.​30 CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Masetti R, Biagi C, Kleinschmidt K, Prete A, Baronio F, Colecchia A et al (2011) Focal nodular hyperplasia of the liver after intensive treatment for pediatric cancer: is hematopoietic stem cell transplantation a risk factor? Eur J Pediatr 170(6):807–812. doi:10.1007/s00431-010-1388-z CrossRefPubMed Masetti R, Biagi C, Kleinschmidt K, Prete A, Baronio F, Colecchia A et al (2011) Focal nodular hyperplasia of the liver after intensive treatment for pediatric cancer: is hematopoietic stem cell transplantation a risk factor? Eur J Pediatr 170(6):807–812. doi:10.​1007/​s00431-010-1388-z CrossRefPubMed
Metadaten
Titel
Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in the DICER1 gene and additional manifestations of the DICER1 syndrome
verfasst von
Julia Fremerey
Stefan Balzer
Triantafyllia Brozou
Joerg Schaper
Arndt Borkhardt
Michaela Kuhlen
Publikationsdatum
28.11.2016
Verlag
Springer Netherlands
Erschienen in
Familial Cancer / Ausgabe 3/2017
Print ISSN: 1389-9600
Elektronische ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-016-9958-5

Weitere Artikel der Ausgabe 3/2017

Familial Cancer 3/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.