DICER1 Syndrome: DICER1 Mutations in Rare Cancers

Robertson, Jake C; Jorcyk, Cheryl L.; Oxford, Julia Thom

doi:10.3390/cancers10050143

Cited by 121 publications

(93 citation statements)

References 106 publications

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“…Dicer1 syndrome—also known as pleuropulmonary blastoma familial susceptibility syndrome—is a rare genetic disorder that is inherited in an autosomal dominant manner [ 39 ] and predisposes the development of both benign and malignant tumors [ 37 , 40 ]. Pathogenic germline mutations of the Dicer (also known as Dicer1 ) gene have been linked to Dicer1 syndrome ( Figure 2 ), whereas mosaic mutations of this gene have also been associated with this condition [ 37 , 41 ]. Mutations in one gene allele lead to an increased risk of tumor development, although, in many cases, this is not sufficient to cause a malignant phenotype.…”

Section: Dicer In Human Diseasesmentioning

confidence: 99%

“…Mutations in one gene allele lead to an increased risk of tumor development, although, in many cases, this is not sufficient to cause a malignant phenotype. The majority of these mutations are located within regions that encode the main protein’s domains ( Figure 3 A,B) and usually result in amino acid alterations and loss of function [ 37 , 39 ].…”

Section: Dicer In Human Diseasesmentioning

confidence: 99%

“…Nuclear Dicer has been associated with transcriptional silencing, RNA post-transcriptional processing, DNA damage response and dsRNA removal [ 1 , 27 , 28 , 29 , 30 ]. Furthermore, other studies have indicated the involvement of Dicer in autophagy and autophagosome formation [ 31 , 32 ], stabilization of passive-site RNAs [ 33 ], antiviral defense [ 34 , 35 , 36 ] and apoptosis [ 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

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Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Theotoki

Pantazopoulou

Georgiou

et al. 2020

IJMS

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Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson’s disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients.

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Section: Dicer In Human Diseasesmentioning

confidence: 99%

Section: Dicer In Human Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Theotoki

Pantazopoulou

Georgiou

et al. 2020

IJMS

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“…Patients with DICER1 syndrome may develop malignant tumors in the lungs (pleuropulmonary blastoma), endocrine organs (multinodular goiter [MNG], ovarian Sertoli-Leydig cell tumor, gynandroblastoma, juvenile granulosa cell tumor, and pituitary blastoma), kidneys (cystic nephroma, Thyroid FNA and DICER1 Mutation/Darbinyan et al Wilms' tumor, anaplastic sarcoma), uterus (embryonal rhabdomyosarcoma), brain (pineoblastoma), and eyes (ciliary body medulloepithelioma). [1][2][3] The DICER1 gene is located on chromosome 14q32.13 and encodes 1922 amino acid protein DICER1, also known as class 3 ribonuclease (RNase-III). The protein contains several distinct domains, including DExD/ Hbox helicase, transactivation response RNA-binding protein binding, RNase IIIa and IIIb, and double-stranded RNA (dsRNA) binding ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology–histopathology correlation in 7 patients

Darbinyan

Morotti

Cai

et al. 2020

Cancer Cytopathology

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BACKGROUND: Germline and somatic mutations of DICER1 have been identified in various types of neoplastic lesions, with germline DICER1 mutation being linked to autosomal dominant hereditary pleiotropic tumor syndrome (DICER1 syndrome). Patients with DICER1 syndrome are at increased risk of developing thyroid disease, including thyroid cancer. The goal of this study was to identify diagnostic cytologic features in thyroid fine-needle aspiration (FNA) samples from patients with DICER1 mutation. METHODS: Cytology cases of thyroid FNA from 7 patients with DICER1 mutation were identified. Clinical, imaging, cytomorphologic, and molecular data were analyzed. RESULTS: Cytologic preparations from reviewed cases showed thyroid lesions of follicular derivation with scant colloid, moderate cellularity, uniform follicular cells with round nuclei and inconspicuous nucleoli arranged in small crowded groups and microfollicles. Follicular neoplasm was diagnosed in 4 cases and follicular lesion of undetermined significance in 3 cases, based on the Bethesda System for Reporting Thyroid Cytopathology. Histopathological analysis of thyroid tissue confirmed neoplastic process in 6 out of 7 cases: follicular carcinoma (FC, 3 cases), papillary thyroid carcinoma (2 cases), poorly differentiated thyroid carcinoma (PDTC, 1 case). Genetic studies identified 3 different somatic variants of DICER1 gene, including transcript consequence c.5428G>T, which was detected in FC and PDTC (and has been described previously in multinodular goiter). CONCLUSION: DICER1 mutation in all analyzed patients was identified as a result of thyroid FNA evaluation, emphasizing the critical role of FNA in the screening of patients with thyroid nodules, proper diagnosis of thyroid disease, and monitoring of patients with DICER1 mutation. Cancer

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“…A body of evidence has indicated that deleterious germline mutations in the DICER1 gene are responsible for DICER1 syndrome, an inherited disorder characterized by an increased frequency of various types of malignant and benign tumors that occur predominantly in infants and young children, the most common and most characteristic of which is pleuropulmonary blastoma [54,55]. It was shown that in cancers associated with DICER1 syndrome as well as other early childhood cancers (e.g., Wilms' tumor), a specific pattern of somatic DICER1 second-hit missense mutations occurs.…”

Section: Introductionmentioning

confidence: 99%

A pan-cancer atlas of somatic mutations in miRNA biogenesis genes

Galka-Marciniak

Urbanek-Trzeciak

Nawrocka

et al. 2020

Preprint

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It is a well-known and intensively studied phenomenon that the levels of many miRNAs are differentiated in cancer. miRNA biogenesis and functional expression are complex processes orchestrated by many proteins cumulatively called miRNA biogenesis proteins. To characterize cancer somatic mutations in the miRNA biogenesis genes and investigate their potential impact on the levels of miRNAs, we analyzed whole-exome sequencing datasets of over 10,000 cancer/normal sample pairs deposited within the TCGA repository. We identified and characterized over 3,600 somatic mutations in 29 miRNA biogenesis genes and showed that some of the genes are overmutated in specific cancers and/or have recurrent hotspot mutations (e.g., SMAD4 in PAAD, COAD, and READ; DICER1 in UCEC; PRKRA in OV; and LIN28B in SKCM). We identified a list of miRNAs whose level is affected by particular types of mutations in either SMAD4, SMAD2, or DICER1 and showed that hotspot mutations in the RNase domains in DICER1 not only decrease the level of 5p-miRNAs but also increase the level of 3p-miRNAs, including many well-known cancer-related miRNAs. We also showed an association of the mutations with patient survival. Eventually, we created an atlas/compendium of miRNA biogenesis alterations providing a useful resource for different aspects of biomedical research.

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DICER1 Syndrome: DICER1 Mutations in Rare Cancers

Cited by 121 publications

References 106 publications

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies

Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology–histopathology correlation in 7 patients

A pan-cancer atlas of somatic mutations in miRNA biogenesis genes

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