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Sci Rep. 2018 Feb 19;8(1):3252. doi: 10.1038/s41598-018-21663-9.

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

Author information

1
Functional Genomics Laboratory, Instituto Nacional de Medicina Genomica, Mexico City, Mexico. jmelendez@inmegen.gob.mx.
2
Facultad de Odontologia, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. gemercadocelis@gmail.com.
3
Functional Genomics Laboratory, Instituto Nacional de Medicina Genomica, Mexico City, Mexico.
4
Group of Reproductive Development and Apomixis, Laboratorio Nacional de Genómica para la Biodiversidad (LANGEBIO), CINVESTAV, Irapuato, Guanajuato, Mexico.
5
Histopathology Unit, Instituto Nacional de Medicina Genomica, Mexico City, Mexico.
6
Hospital Infantil de Mexico, Mexico City, Mexico.
7
Instituto Nacional de Pediatria, Mexico City, Mexico.
8
Epigenomics Laboratory, Instituto Nacional de Medicina Genomica, Mexico City, Mexico.
9
Facultad de Odontologia, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.
10
Clinical Area, Instituto Nacional de Medicina Genomica, Mexico City, Mexico.

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.

PMID:
29459759
PMCID:
PMC5818504
DOI:
10.1038/s41598-018-21663-9
[Indexed for MEDLINE]
Free PMC Article

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