DICER1 Syndrome: A New Cancer Syndrome

Abstract

Recently, germline mutations of DICER1 have been identified in patients with rare neoplasms suggesting the existence of a newly discovered cancer prone syndrome. Initially, DICER1 mutations were identified in patients with familial pleuropulmonary blastoma. Subsequently, additional manifestations of the syndrome have been identified including cystic nephroma, medulloepithelioma, Sertoli-Leydig cell tumor and others. The DICER1 gene encodes an enzyme that is involved in the biogenesis of microRNAs. The entire tumor spectrum and the respective tumor risks are unknown. We are in the process of launching a natural history study aimed at identifying more information on this new cancer syndrome.

MicroRNA biogenesis pathways in cancer

“…Interestingly, modelling of PPB in mice supports the idea that Dicer1 deletion in the distal airway epithelium causes non-cellautonomous tumour initiation, whereby Dicer1 loss in the epithelium causes the underlying mesenchymal cells to be malignantly transformed 81 . DICER1 mutations are frequently found in different types of inherited tumours: PPB 16,80–84 , non-epithelial ovarian cancer 18,84,85 , Wilms tumour 22,86,87 , pituitary blastoma 88 , cystic nephroma 89 , rhabdomyosarcoma 90 and others 91 (see Supplementary information S1 (table)). As a result, patients harbouring these DICER1 mutations have reduced DICER1 expression and/or impaired DICER1 function, which cause the abnormal expression of miRNAs and contribute to the pathogenesis of cancer.…”

The Roles of MicroRNAs and Protein Components of the MicroRNA Pathway in Lung Development and Diseases

“…Recently, DICER1 mutations have been associated with cystic nephroma, medulloepithelioma, and Sertoli-Leydig cell tumors (65)(66)(67). The early stages of PPB feature cystic expansion of airways lined by benign-appearing epithelium.…”

Ovarian Sertoli Leydig cell tumours in children and adolescents: An analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT)

“…These are associated with pleuropulmonary blastoma or familial multinodular goitre or rarely even thyroid cancer, making SLCT a part of a tumour predisposition syndrome [17].…”