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Fam Cancer. 2017 Jul;16(3):401-405. doi: 10.1007/s10689-016-9958-5.

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

Author information

1
Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, Moorenstr. 5, 40225, Düsseldorf, Germany.
2
Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
3
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.

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.

KEYWORDS:

DICER1 germline mutation; DICER1-syndrome; Embryonal rhabdomyosarcoma; Focal nodular hyperplasia; Frameshift; Medulloepithelioma; Pleuropulmonary blastoma; Renal cysts

PMID:
27896549
DOI:
10.1007/s10689-016-9958-5
[Indexed for MEDLINE]

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