Identification of novel cyclin gene fusion transcripts in endometrioid ovarian carcinomas. Issue 6 (25th April 2018)

• Record Type: Journal Article
• Authors: Agostini, Antonio; Brunetti, Marta; Davidson, Ben; Göran Tropé, Claes; Heim, Sverre; Panagopoulos, Ioannis; Micci, Francesca
• Is Part Of: International journal of cancer. Volume 143:Issue 6(2018)
• Page Start: 1379
• Page End: 1387
• Publication Date: 2018-04-25
• Subjects: ovarian carcinoma -- fusion transcript -- NRG4 -- cyclin -- CCNL2; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31418
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Chimeric genes formed by fusion of previously separate genes are associated with many malignant tumors, but rare in ovarian cancer. Here the authors performed transcriptome sequencing of different types of ovarian tumors and identify novel fusion genes, involving cyclin genes, the master regulators of the cell cycle. As most of these fusions were found in ovarian cancer of the endometroid type, which represent about 10% of all ovarian cancers, the data point to a novel role of cyclin deregulation in this specific cancer subtype.