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

Abstract

Gene fusions are thought to be driver mutations in multiple cancers and are an important factor for poor patient prognosis. Most of them appear in specific cancers, thus satisfactory strategies can be developed for the precise treatment of these types of cancer. Currently, there are few targeted drugs to treat gynecologic tumors, and patients with gynecologic cancer often have a poor prognosis because of tumor progression or recurrence. With the application of massively parallel sequencing, a large number of fusion genes have been discovered in gynecologic tumors, and some fusions have been confirmed to be involved in the biological process of tumor progression. To this end, the present article reviews the current research status of all confirmed fusion genes in gynecologic tumors, including their rearrangement mechanism and frequency in ovarian cancer, endometrial cancer, endometrial stromal sarcoma, and other types of uterine tumors. We also describe the mechanisms by which fusion genes are generated and their oncogenic mechanism. Finally, we discuss the prospect of fusion genes as therapeutic targets in gynecologic tumors.

Identification of a Novel Oncogenic Fusion Gene SPON1-TRIM29 in Clinical Ovarian Cancer That Promotes Cell and Tumor Growth and Enhances Chemoresistance in A2780 Cells

“…In clinic, ALK inhibitors are successfully used to treat non-small cell lung cancer, in which ALK fusion genes were found in approximately 5% [ 25 ]. In terms of ovarian cancer, a number of fusion genes has also been identified [ 26 ]; however, the elucidation of their functions and mechanisms is limited only in several fusion genes, including SLC25A40-ABCB1 , MAN2A1-FER , BCAM-AKT2 , FHL2-GLI2 , YWHAE-FAM22A , JAZF1-SUZ12 , and FGFR3-TACC3 [ 27 , 28 , 29 ], and the clinical application of these findings is not available.…”

Exploring the Relationship between Fusion Genes and MicroRNAs in Cancer

“…Cancer-specific fusion oncogenes are specifically expressed in cancer cells but not in normal cells [2]. Fusion genes are true genetic drivers of oncogenesis [38,47] that are functionally responsible for driving the initiation and progression of many tumors [48,49]. In a few cancers, the fusion gene will be the only driver of mutation for that particular cancer [49].…”

“…In a few cancers, the fusion gene will be the only driver of mutation for that particular cancer [49]. Fusion genes are cancer-specific etiological aberrations correlated to the tumor phenotype [48,50,51]. Since these genes have diverse features and characteristics, they are typically used as drug targets for precision oncotherapies [2,38], however, it is unequivocal that not all fusion genes contribute to carcinogenesis [3], as these genes also play a role in normal physiological functions [52].…”

Nasopharyngeal Carcinoma Progression: Accumulating Genomic Instability and Persistent Epstein–Barr Virus Infection

“…Chromosome breakage and gene rearrangement occur when an organism is exposed to pathological or harmful external environmental factors, resulting in the formation of new gene fragments that lead to the development of malignant neoplastic diseases [ 36 ]. Fusion genes with both breakage and rearrangement have been detected in NPC, such as UBR5 - ZNF423 , RARS - MAD1L1 , and FGFR3 - TACC3 [ 37 , 38 , 39 ].…”