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N Engl J Med. 2019 May 9;380(19):1834-1842. doi: 10.1056/NEJMoa1812169.

Mesenchymal Hamartoma of the Liver and DICER1 Syndrome.

Author information

1
From the Departments of Human Genetics (M.A.-R., M.K.W., W.D.F.), Pharmacology (D.P.), Oncology (M.R.F., W.D.F.), and Biochemistry (M.R.F.), and the Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital (M.A.-R., D.P., N.S., M.K.W., M.R.F., W.D.F.), McGill University, the Department of Pathology, Montreal Children's Hospital (V.-H.N.), the Department of Radiology (K.M.), and the Cancer Research Program, Research Institute (W.D.F.), McGill University Health Centre, and the Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine (D.B.-D.S.) - all in Montreal; the Department of Pediatrics, Endocrinology Unit, Sapienza University, Rome (M.S.), and Centro Diagnostico Italiano, Milan (S.Z.) - both in Italy; the Department of Pediatrics and Adolescent Medicine, Faculty of Medicine (M.K.), and the Institute for Diagnostic and Interventional Radiology, Faculty of Medicine (J.M.), Georg-August University, Göttingen, the Department of Pediatric Surgery, St. Bernward Krankenhaus Hildesheim, Hildesheim (S.G.), and the Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm (R.W., C.L., R.S.) - all in Germany; and Minneapolis (J.R.P.).

Abstract

Mesenchymal hamartoma of the liver (MHL) is a benign tumor affecting children that is characterized by a primitive myxoid stroma with cystically dilated bile ducts. Alterations involving chromosome 19q13 are a recurrent underlying cause of MHL; these alterations activate the chromosome 19 microRNA cluster (C19MC). Other cases remain unexplained. We describe two children with MHLs that harbored germline DICER1 pathogenic variants. Analysis of tumor tissue from one of the children revealed two DICER1 "hits." Mutations in DICER1 dysregulate microRNAs, mimicking the effect of the activation of C19MC. Our data suggest that MHL is a new phenotype of DICER1 syndrome. (Funded by the Canadian Institutes of Health Research and others.).

PMID:
31067372
DOI:
10.1056/NEJMoa1812169
[Indexed for MEDLINE]

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