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Genes Chromosomes Cancer. 2018 May;57(5):223-230. doi: 10.1002/gcc.22523. Epub 2018 Feb 10.

Multiple DICER1-related tumors in a child with a large interstitial 14q32 deletion.

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Department of Human Genetics, McGill University, Montréal, Québec, Canada.
Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montréal, Québec, Canada.
Institute of Human Genetics, University of Ulm and University of Ulm Medical Center, Ulm, Germany.
Department of Pathology, CHU Sainte Justine, Quebec, Canada.
Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
The Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida, USA.
Division of Clinical Genetics, Center for Genomic Medicine, Miami Cancer Institute, Miami, Florida, USA.
Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
Department of Pathology, Hospital Infantil de San José, Bogotá, Colombia.
Department of Pediatric Radiology, Texas Children's Hospital, Houston, Texas, USA.
Department of Pathology, Sidra Medicine, Doha, Qatar.
Minneapolis, Minnesota, USA.
Department of Medical Genetics, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada.


Germ-line interstitial deletions involving the 14q32 chromosomal region, resulting in 14q32 deletion syndrome, are rare. DICER1 is a recently described cancer-predisposition gene located at 14q32.13. We report the case of a male child with a ∼5.8 Mbp 14q32.13q32.2 germ-line deletion, which included the full DICER1 locus. We reviewed available clinical and pathological material, and conducted genetic analyses. In addition to having congenital dysmorphic features, the child developed multiple DICER1 syndrome-related tumors before age 5 y: a pediatric cystic nephroma (pCN), a ciliary body medulloepithelioma (CBME), and a small lung cyst (consistent with occult pleuropulmonary blastoma Type I/Ir cysts seen in DICER1 mutation carriers). He also developed a cerebral spindle-cell sarcoma with myogenous differentiation. Our investigations revealed that the deletion encompassed 31 protein-coding genes. In addition to the germ-line DICER1 deletion, somatic DICER1 RNase IIIb mutations were found in the CBME (c.5437G > A, p.E1813K), pCN (c.5425G > A, p.G1809R), and sarcoma (c.5125G > A, p.D1709N). The sarcoma also harbored a somatic TP53 mutation: c.844C > T, p.R282W. Additional copy number alterations were identified in the CBME and sarcoma using an OncoScan array. Among the 8 cases with molecularly-defined 14q32 deletions involving DICER1 and for whom phenotypic information is available, our patient and one other developed DICER1-related tumors. Biallelic DICER1 mutations have not previously been reported to cause cerebral sarcoma, which now may be considered a rare manifestation of the DICER1 syndrome. Our study shows that DICER1-related tumors can occur in children with 14q32 deletions and suggests surveillance for such tumors may be warranted.

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