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Oncotarget. 2019 Jun 4;10(38):3614-3624. doi: 10.18632/oncotarget.26942. eCollection 2019 Jun 4.

Molecular characterization of carcinosarcomas arising in the uterus and ovaries.

Author information

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.
#
Contributed equally

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:

gene expression; miRNA expression; mutational analysis; ovarian carcinosarcomas; uterine carcinosarcomas

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