Perspective Insight into Future Potential Fusion Gene Transcript Biomarker Candidates in Breast Cancer

Abstract

Next generation sequencing has accelerated the discovery of a variety of new fusion gene types in clinical breast cancer samples by analyzing cancer genomes and transcriptomes. Although previous studies have focused on a few clinically validated oncogenic fusion genes as diagnostic and therapeutic targets in breast cancer, a perspective consideration has not been given thus far for a plethora of breast cancer fusion genes, which are being newly identified at an overwhelmingly increasing pace. In this perspective review, we discuss diverse fusion gene types recently identified in a variety of breast cancer subtypes, including breast clinical cancer samples in TCGA (The Cancer Genome Atlas) database. This perspective review will confer fresh and promising guidance onto breast cancer surgeons, clinical oncologists, and tumor biologists in determining research directions for seeking and developing novel fusion gene biomarkers for breast cancer diagnostics and therapeutic treatment in upcoming years.

SVExpress: identifying gene features altered recurrently in expression with nearby structural variant breakpoints

“…Twenty-five fusions were detected in more than one cell line (Fig. 4 c), a number of which have previously been detected in human tumors, including RPS6KB1 - VMP1 [ 15 ], WWOX - VAT1L [ 16 ], ASCC1 - MICU1 [ 17 ], ESR1 - CCDC170 [ 18 ], FHOD3 - MOCOS [ 19 ], IMMP2L - DOCK4 [ 19 ], LRBA - SH3D19 [ 19 ], PPFIBP1 - SMCO2 [ 19 ], PVT1 - CASC11 [ 20 ], PVT1 - CASC8 [ 20 ], PXN - PLA2G1B [ 21 ], TBC1D22A - GRAMD4 [ 19 ], and TRMT11 - NCOA7 [ 19 ]. The well-known TMPRSS2 gene fusions in prostate cancer [ 22 ] were also detected in CCLE data by RNA-seq STAR-fusion algorithm, in VCAP and NCIH660 cell lines, but these cell lines did not have corresponding WGS data for SV calling.…”

Promising Prognosis Marker Candidates on the Status of Epithelial–Mesenchymal Transition and Glioma Stem Cells in Glioblastoma

“…EMT also contributes to tumor invasion, heterogeneity, chemoresistance, and robustness in reprogrammed gene expression that enables morphological and functional dedifferentiation into CSCs from differentiated tumor cells [39]. Dysregulation of splicing factors and tumor-specific isoforms frequently occurs in human tumors, indicating the importance of post-transcriptional regulation, including alternative splicing and/or gene fusion [38,42,43]. Thus, it is considered that EMT and stem cell differentiation, including dedifferentiation into CSCs, are closely related to cancer development and progression.…”

Protein kinase C fusion proteins are paradoxically loss of function in cancer

“…Given that PKC is the most abundantly fused AGC kinase and the fusions were detected in a multitude of cancers, we sought to determine how these fusions might affect PKC signaling and contribute to tumorigenesis. To this end, we selected three 3' fusions (TANC2-PRKCA, SLC44A1-PRKCA, and GGA2-PRKCB) and one 5' fusion (PRKCA-CDH8) in this study for further analysis (18,(34)(35)(36)(37)41).…”

“…For our biochemical analyses, we selected the fusion PRKCA-CDH8, originally detected in breast cancer (Fig. 6A) (18,30,41). PRKCA-CDH8 translates to a protein containing the first 306 amino acid residues of PKCα fused to the last 715 residues of Cadherin-8 (CDH8).…”