Further evidence that full gene deletions of <i>DICER1</i> predispose to DICER1 syndrome

Kock, Leanne de; Hillmer, Morten; Wagener, Rabea; Soglio, Dorothée Bouron‐Dal; Sabbaghian, Nelly; Siebert, Reiner; Priest, John R.; Miller, Michal; Foulkes, William D.

doi:10.1002/gcc.22728

Cited by 8 publications

(5 citation statements)

References 7 publications

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“…This lowers the odds of all events coinciding and could explain the low penetrance of DICER1 syndrome 34 . Exceptions to this model include pineoblastomas, where loss‐of‐heterozygosity (LOH) is frequently found in the second allele, 40,41 individuals with de novo germline DICER1 variants 42 or with large germline deletions 43‐46 and DICER1 mosaics 34,47,48 …”

Section: Dicer1 Function Dicer1 Syndrome and Molecular Geneticsmentioning

confidence: 99%

DICER1‐associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing

Apellaniz-Ruiz

McCluggage

Foulkes

2020

Genes Chromosomes & Cancer

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Gynecologic sarcomas are uncommon neoplasms, the majority occurring in the uterus. Due to the diverse nature of these, the description of “new” morphological types and the rarity of some of them, pathological diagnosis and treatment is often challenging. Finding genetic alterations specific to, and frequently occurring, in a certain type can aid in the diagnosis. DICER1 is a highly conserved ribonuclease crucial in the biogenesis of microRNAs and mutations in DICER1 (either somatic or germline) have been detected in a wide range of sarcomas including genitourinary embryonal rhabdomyosarcomas (ERMS) and adenosarcomas. Importantly, DICER1‐associated sarcomas share morphological features irrespective of the site of origin such that the pathologist can strongly suspect a DICER1 association. A review of the literature shows that almost all gynecologic ERMS reported (outside of the vagina) harbor DICER1 alterations, while approximately 20% of adenosarcomas also do so. These two tumor types exhibit significant morphological overlap and DICER1 tumor testing may be helpful in distinguishing between them, because a negative result makes ERMS unlikely. Given that germline pathogenic DICER1 variants are frequent in uterine (corpus and cervix) ERMS and pathogenic germline variants in this gene cause a hereditary cancer predisposition syndrome (DICER1 syndrome), patients diagnosed with these neoplasms should be referred to medical genetic services. Cooperation between pathologists and geneticists is crucial and will help in improving the diagnosis and management of these uncommon sarcomas.

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Section: Dicer1 Function Dicer1 Syndrome and Molecular Geneticsmentioning

confidence: 99%

DICER1‐associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing

Apellaniz-Ruiz

McCluggage

Foulkes

2020

Genes Chromosomes & Cancer

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“…While most individuals with DICER1 syndrome are heterozygous for a germline loss‐of‐function DICER1 pathogenic variant, other predisposing DICER1 alterations have also been documented. These include deletion of the entire DICER1 locus (de Kock, Geoffrion, et al, ; de Kock et al, ; Herriges et al, ; van Engelen et al, ), in‐ and out‐of‐frame intragenic deletions involving one or more exons (Apellaniz‐Ruiz et al, ; Brenneman et al, ; Sabbaghian et al, ), and somatic mosaicism, which is observed in a small fraction of syndromic patients (Brenneman et al, ; de Kock et al, ; Klein et al, ). Individuals with mosaicism for loss‐of‐function mutations tend to exhibit one or two foci of disease; in contrast, mosaicism for RNase IIIb hotspot mutations results in a greater number of disease foci at significantly younger ages than is typical (Brenneman et al, ; de Kock et al, ).…”

Section: Introductionmentioning

confidence: 99%

Ten years of DICER1 mutations: Provenance, distribution, and associated phenotypes

2019

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DICER1 syndrome is a pleiotropic tumor predisposition syndrome characterized by a distinctive constellation of neoplastic and dysplastic lesions, which are generally rare and affect children and young adults. Germline pathogenic variants in the DICER1 gene are the underlying cause of the syndrome; variants are typically inherited in an autosomal dominant pattern but may arise de novo in the germline or in a somatic mosaic distribution. The encoded DICER1 protein is a key component of the microRNA processing pathway. In this Mutation Update, we present a comprehensive review of all DICER1 genetic alterations reported in articles published before January 31st, 2019. A total of 1,136 DICER1 alterations were catalogued from 808 individuals and the tumors that occurred in these persons. We provide an inventory of these DICER1 alterations and discuss them with respect to their provenance, distribution across the gene, associated phenotypes and ages of onset, and penetrance. We also address approaches to classification of DICER1 variants of uncertain significance and discuss the clinical significance of DICER1 variant identification.

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“…Only a few children with SLCT and thyroid pathology, with or without associating genitourinary ERMS, has been reported to date. [6][7][8][9][10][11] Our patient developed embryonal RMS of the cervix and was treated by endoscopic surgery and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Sertoli-Leydig cell tumor, thyroid follicular carcinoma and rhabdomyosarcoma of the uterine cervix in a prepubertal girl with pathogenic germline variant in DICER1 gene

et al. 2021

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Background. DICER1 syndrome is a hereditary cancer predisposition syndrome which is related DICER1 gene and may present a variety of manifestations.Case. A prepubertal girl with ovarian Sertoli-Leydig cell tumor, thyroid follicular carcinoma, embryonal rhabdomyosarcoma of the cervix and lung cyst is presented. Genetic analysis demonstrated mutation (c.3377delC, c.71delC) in 14q32.13 loci and confirmed the diagnosis of DICER1 syndrome. Conclusion.The case is presented to emphasize the importance of early diagnosis of alterations in DICER1 gene and close follow-up for the development of DICER1 syndrome related pathologies, and necessity for genetic evaluation of the family.

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Further evidence that full gene deletions of DICER1 predispose to DICER1 syndrome

Cited by 8 publications

References 7 publications

DICER1‐associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing

DICER1‐associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing

Ten years of DICER1 mutations: Provenance, distribution, and associated phenotypes

Sertoli-Leydig cell tumor, thyroid follicular carcinoma and rhabdomyosarcoma of the uterine cervix in a prepubertal girl with pathogenic germline variant in DICER1 gene

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