Identification of novel cyclin gene fusion transcripts in endometrioid ovarian carcinomas

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.

Transcript Complexity and New Insights of Restorer Line in CMS-D8 Cotton Through Full-Length Transcriptomic Analysis

“…Our results identified 7,234 AS events, 1,667 APA, and 114 fusion transcripts that exposed the complexity of transcripts in R line. The functional verification of fusion transcripts has been carried out in some studies in human diseases (Agostini et al, 2018;Siegfried et al, 2019), but rarely Previous studies reported that the restoration of function conditioned by one dominant restorer Rf 2 gene in R line of CMS-D8 cotton (Zhang and Stewart, 2001a). At the present, there is no report about the gene expression profiles affected by the Rf 2 in R line.…”

“…Our results identified 7,234 AS events, 1,667 APA, and 114 fusion transcripts that exposed the complexity of transcripts in R line. The functional verification of fusion transcripts has been carried out in some studies in human diseases ( Agostini et al, 2018 ; Siegfried et al, 2019 ), but rarely reported in plants. This study verified the existence of the fusion transcript, m64033_190821_201011/87884027/cc but unable to study function of this fusion transcript.…”

Mesenchymal PLAG1 Tumor With PCMTD1-PLAG1 Fusion in an Infant: A New Type of “Plagoma”

“…1 PLAG1 fusions have been reported in different tumors, including lipoblastoma, 6 and PCMTD1 fusions have recently been associated with ovarian endometrioid carcinoma. 2 Chung et al 7 recently reported 3 cases of a unique soft tissue tumor in young children with purely fibromyxoid histology associating PLAG1 fusion variants (in 2 cases, a YWHAZ-PLAG1 gene fusion was detected, and in the third, an EEF1A1-PLAG1 gene fusion was detected). These 3 cases presented distinct biphasic morphology with pale myxoid nodules separated by pink fibroblastic areas and were immunohistochemically positive for desmin and CD34.…”

“…Pleomorphic adenoma gene 1 ( PLAG1 ) encodes a zinc finger protein inducing the expression of a variety of genes implicated in regulating cell proliferation, 1 and PCMTD1 [protein- l -isoaspartate ( d -aspartate) O-methyltransferase domain containing 1] has recently been related to the development of certain carcinomas. 2 Herein, we describe a mesenchymal skin neoplasm with a novel PCMTD1-PLAG1 fusion.…”

Fusion genes in gynecologic tumors: the occurrence, molecular mechanism and prospect for therapy

“…The fusion genes that have been identified in ovarian cancer are PCMTD1-CCNL2, ANXA5-CCNA2, CCN4-NRG4, SLC25A40-ABCB1, DPP9-PPP6R3, MAN2A1-FER, CDKN2D-WDFY2, BCAM-AKT2, and FHL2-GLI2. These fusion genes involve cyclin family genes, multi-drug resistance related MDR/TAP subfamily genes, tyrosine kinase family genes, and AKT signaling pathway-related genes [ 52 ].…”