文章基本信息

标题：Genomics of a pediatric ovarian fibrosarcoma. Association with the DICER1 syndrome
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作者：Jorge Melendez-Zajgla ; Gabriela E. Mercado-Celis ; Javier Gaytan-Cervantes 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：3252
DOI：10.1038/s41598-018-21663-9
语种：English
出版社：Springer Nature
摘要：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.