Dataset Information

Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1 syndrome.

ABSTRACT: Ovarian fibrosarcomas are extremely rare tumors with little genomic information available to date. In the present report we present the tumoral exome and transcriptome and the germinal exome of an ovarian fibrosarcoma from a 9-years old child. We found a paucity of mutations (0.77/Mb) and CNV alterations. Of these, the most relevant were a point mutation in the metal-binding site of the microRNA-processing DICER1 enzyme and a frame-shift alteration in the tumor suppressor gene NF1. We validated a germinal truncating mutation in DICER1, which was consistent with a DICER1 Syndrome diagnosis, providing the first example of an ovarian fibrosarcoma as the presenting neoplasia in this syndrome. Network and enrichment analyses showed that both a mesenchymal signature and a Hedgehog cascade could be driving the progression of this tumor. We were also able to find a global lincRNA deregulation, as the number of lincRNAs transcripts expressed in the tumor was decreased, with a concomitant upregulation of previously described non-coding transcripts associated with cancer, such as MALAT1, MIR181A1HG, CASC1, XIST and FENDRR. DICER1 Syndrome should be considered as a possible diagnosis in children ovarian fibrosarcoma. The role of lncRNAs in neoplasias associated with DICER1 alterations need to be studied in more detail.

SUBMITTER: Melendez-Zajgla J

PROVIDER: S-EPMC5818504 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1 syndrome.

Melendez-Zajgla Jorge J Mercado-Celis Gabriela E GE Gaytan-Cervantes Javier J Torres Amada A Gabiño Nayeli Belem NB Zapata-Tarres Martha M Juarez-Villegas Luis Enrique LE Lezama Pablo P Maldonado Vilma V Ruiz-Monroy Karen K Mendoza-Caamal Elvia E

Scientific reports 20180219 1

Ovarian fibrosarcomas are extremely rare tumors with little genomic information available to date. In the present report we present the tumoral exome and transcriptome and the germinal exome of an ovarian fibrosarcoma from a 9-years old child. We found a paucity of mutations (0.77/Mb) and CNV alterations. Of these, the most relevant were a point mutation in the metal-binding site of the microRNA-processing DICER1 enzyme and a frame-shift alteration in the tumor suppressor gene NF1. We validated ...[more]

PMID: 29459759

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Project description:ImportancePediatric pseudotumor cerebri syndrome pathophysiology is complex and not well delineated. Therefore, it is important to identify potential contributors or targets underlying the primary pathogenesis for its development.ObjectiveTo report cases highlighting the association of pediatric pseudotumor cerebri syndrome with adrenal insufficiency.Design, setting, and participantsThis noncontrolled, observational case series included pediatric patients diagnosed with pseudotumor cerebri syndrome and adrenal insufficiency at an urban academic children's hospital in Houston, Texas, from June 2015 to October 2019.Main outcomes and measuresMonitoring optic nerve edema by clinical examination, fundus photography, and optical coherence topography images of the optic nerve.ResultsData were collected from 5 pediatric patients (age range, 5-10 years) diagnosed with pseudotumor cerebri syndrome and adrenal insufficiency. One was a girl; all were White and prepubertal. Three patients had unrecognized glucocorticoid exposure. All patients had bilateral optic nerve edema that was initially treated with acetazolamide or topiramate, but cortisol functional testing by either 8 am cortisol or cosyntropin stimulation tests revealed a diagnosis of central adrenal insufficiency. Treatment with physiological doses of hydrocortisone resulted in resolution of optic nerve edema and clinical symptoms of pseudotumor cerebri syndrome, as well as a shorter time receiving medical therapy.Conclusions and relevanceIn this case series, adrenal insufficiency was associated with both primary and secondary prepubertal pediatric pseudotumor cerebri syndrome. As a potential target specific to causative mechanism, physiologic hydrocortisone therapy resolved the condition. To date, there remains a global unawareness among clinicians about the suppressive outcome that glucocorticoids may have on the developing hypothalamic-pituitary-adrenal axis, resulting in adrenal insufficiency and so-called episodic pseudotumor cerebri syndrome in young children. Ophthalmologists and pediatric subspecialists should implement cortisol testing via either 8 am cortisol or cosyntropin stimulation tests at initial evaluation of all children with pseudotumor cerebri syndrome and risk factors for adrenal insufficiency, no predisposing causes, or nonresponse to conventional treatment. Further management and treatment should be in combination with ophthalmology and endocrine services.

Dataset Information

Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1 syndrome.

Publications

Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1 syndrome.

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