Molecular characterization of carcinosarcomas arising in the uterus and ovaries
Open Access
- 4 June 2019
- journal article
- Published by Impact Journals, LLC in Oncotarget
- Vol. 10 (38), 3614-3624
- https://doi.org/10.18632/oncotarget.26942
Abstract
// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Marta Brunetti1,2,*, Antonio Agostini1,*, Julie Staurseth1, Ben Davidson2,3, Sverre Heim1,3 and Francesca Micci1 1 Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway 2 Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway 3 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway * These authors contributed equally to this work Correspondence to: Francesca Micci, email: francesca.micci@labmed.uio.no Keywords: uterine carcinosarcomas; ovarian carcinosarcomas; mutational analysis; gene expression; miRNA expression Received: March 06, 2019 Accepted: April 29, 2019 Published: June 04, 2019 ABSTRACT Gynaecological carcinosarcomas are rare biphasic tumours which are highly aggressive. We performed molecular investigations on a series of such tumours arising in the uterus (n = 16) and ovaries (n = 10) to gain more information on their mutational landscapes and the expression status of the genes HMGA1/2, FHIT, LIN28A, and MTA1, the pseudogenes HMGA1P6 and HMGA1P7, and the miRNAs known to influence expression of the above-mentioned genes. In uterine carcinosarcomas (UCS), we identified mutations in KRAS, PIK3CA, and TP53 with a frequency of 6%, 31%, and 75%, respectively, whereas in ovarian carcinosarcomas (OCS), TP53 was the only mutated gene found (30%). An inverse correlation was observed between overexpression of HMGA1/2, LIN28A, and MTA1 and downregulation of miRNAs such as let-7a, let-7d, miR26a, miR16, miR214, and miR30c in both UCS and OCS. HMGA2 was expressed in its full length in 14 UCS and 9 OCS; in the remaining tumours, it was expressed in its truncated form. Because FHIT was normally expressed while miR30c was downregulated, not both downregulated as is the case in several other carcinomas, alterations of the epithelial-mesenchymal transition through an as yet unknown mechanism seems to be a feature of carcinosarcomas.Keywords
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