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Int J Cancer. 2018 Sep 15;143(6):1379-1387. doi: 10.1002/ijc.31418. Epub 2018 Apr 25.

Identification of novel cyclin gene fusion transcripts in endometrioid ovarian carcinomas.

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
Faculty of Medicine, University of Oslo, Oslo, Norway.
4
Department of Gynecology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
5
Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Norway.

Abstract

Formation of fusion genes is pathogenetically crucial in many solid tumors. They are particularly characteristic of several mesenchymal tumors, but may also be found in epithelial neoplasms. Ovarian carcinomas, too, may harbor fusion genes but only few of these were found to be recurrent with a rate ranging from 0.5 to 5%. Because most attempts to find specific and recurrent fusion transcripts in ovarian carcinomas focused exclusively on high-grade serous carcinomas, the situation in the other carcinoma subgroups remains largely uninvestigated as far as fusion genes are concerned. We performed transcriptome sequencing on a series of 34 samples from ovarian tumors that included borderline, clear cell, mucinous, endometrioid, low-grade and high-grade serous carcinomas in search of fusion genes typical of these subtypes. We found a total of 24 novel fusion transcripts. The PCMTDI-CCNL2 fusion transcript, which involves a member of the cyclin family, was found recurrently involved but only in endometrioid carcinomas (4 of 18 tumors; 22%). We also found three additional fusion transcripts involving genes belonging to the cyclin family: ANXA5-CCNA2 and PDE4D-CCNB1 were detected in two endometrioid carcinomas, whereas CCNY-NRG4 was identified in a clear cell carcinoma. The recurrent involvement of CCNL2 in four fusions and of three other genes of the cyclin family in three additional transcripts hints that deregulation of cyclin genes is important in the pathogenesis of ovarian carcinomas in general but of endometrioid carcinomas particularly.

KEYWORDS:

CCNL2; NRG4; cyclin; fusion transcript; ovarian carcinoma

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