PRJNA280103
CDKN2D-WDFY2 is a cancer-specific fusion gene recurrent in high-grade serous ovarian carcinoma
Recurrent gene fusions have been described in many tumor types but have been difficult to identify in high-grade serous ovarian cancer (HG-SC), a cancer known for its significant heterogeneity and genome instability. Here, we combined high-throughput transcriptome sequencing with experimental validation to identify a cancer-specific and inter-chromosomal fusion gene CDKN2D-WDFY2 that is recurrent at 25% among HG-SC patients. CDKN2D is a cell-cycle modulator that is also involved in DNA repair while WDFY2 is known to modulate AKT interactions with its substrates. Transfection of the fusion construct led to loss of CDKN2D and WDFY2 protein expression, and gain of an aberrant short WDFY2 protein isoform under the control of CDKN2D promoter. This short WDFY2 in turn led to marked alterations of the PI3K/AKT pathway, a signaling pathway with major implications in oncogenesis. Thus, CDKN2D-WDFY2 fusion could be an important molecular signature for understanding and classifying sub-lineages among heterogenous HG-SC.