DICER1 Syndrome and Cancer Predisposition: From a Rare Pediatric Tumor to Lifetime Risk

Abstract

DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene. The risk to present a neoplasm before the age of 10 years is 5.3 and 31.5% before the age of 60. DICER1 variants have been associated with a syndrome involving familial pleuropulmonary blastoma (PPB), a rare malignant tumor of the lung, which occurs primarily in children under the age of 6 years and represents the most common life-threatening manifestation of DICER1 syndrome. Type I, II, III, and Ir (type I regressed) PPB are reported with a 5-year overall survival ranging from 53 to 100% (for type Ir). DICER1 gene should be screened in all patients with PPB and considered in other tumors mainly in thyroid neoplasms (multinodular goiter, thyroid cancer, adenomas), ovarian tumors (Sertoli-Leydig cell tumor, sarcoma, and gynandroblastoma), and cystic nephroma. A prompt identification of this syndrome is necessary to plan a correct follow-up and screening during lifetime.

Modulation of miRISC-Mediated Gene Silencing in Eukaryotes

“…Both germline and somatic mutations in the DICER gene have been found in various cancers ( Foulkes et al, 2014 ). Dicer1 syndrome is a rare genetic condition where specific mutations in the dicer gene predispose the patient for hereditary cancers ( Caroleo et al, 2020 ). Only a third of Dicer1 pathogenic variant carriers present neoplasms during their life, suggesting there may be multiple additive events needed to create the neoplasm ( Foulkes et al,.…”

“…Only a third of Dicer1 pathogenic variant carriers present neoplasms during their life, suggesting there may be multiple additive events needed to create the neoplasm ( Foulkes et al,. 2014 ; Stewart et al, 2019 ; Caroleo et al, 2020 ). As the type of mutation in DICER gene can vary, future work will be needed to uncover how the specific type of mutation will alter the role of Dicer in recognition, binding, and processing of pre-miRNAs in addition to identifying the other events that may increase the chances of neoplasms occurring.…”

Pleuropulmonary Blastoma (PPB) in Child with DICER1 Mutation: The First Case Report in the State of Qatar

“…The risk of life-long tumor formation in individuals with DICER1 syndrome is only moderately increased compared with tumor risk in the general population. However, close follow-up and frequent screening for tumor development in asymptomatic subjects with identified DICER1 gene have been recommended [15].…”

Towards an integrative understanding of cancer mechanobiology: calcium, YAP, and microRNA under biophysical forces

“…307 In the DICER1 gene, somatic 'hotspot' mutations at the four catalytic residues in the RNase IIIb domain (D1709, E1705, E1813, D1810) and one catalytic residue in the RNase IIIa domain (G1809) were identified in ovarian sex cord-stromal tumors, pediatric tumors and endometrial tumors. [308][309][310] Likewise, 15 RNase IIIb hotspot in uterine corpus endometrial carcinoma (UCEC) cases show down-regulation of specific 5p miRNAs. 311 AGO2, the only slicing protein in the AGO family that cleave miRNA duplexes, plays a vital role in the accumulation of mature miRNAs.…”