OCRF Research Identifies Fusion Gene Common in Ovarian Cancer

(April 7, 2014) A group of OCRF-funded researchers at Baylor College of Medicine have found a “fusion gene” that is present in 20% of high grade serous ovarian cancer patients.  The finding, which was published in PLOS Genetics, was supported in part by OCRF grants to Martin Matzuk, MD, PhD, Shannon Hawkins, MD, PhD, and Laising Yen, PhD.

High-grade serous carcinoma (HG-SC) is the most common subtype of ovarian cancer observed in women. This subtype of ovarian cancer is typically detected at advanced stages due to lack of effective early screening tools. Characterization of HG-SC is further complicated by the significant variation displayed by this cancer among patients. Discovery of specific molecular signatures that are unique yet prevalent among HG-SC is essential for understanding the underlying pathogenesis of HG-SC and for designing personalized treatment.

Fusion genes, formed from two separate parental genes as a result of chromosomal rearrangement, could represent such specific molecular signatures. In particular, a fusion gene that is cancer-specific and occurs in high frequency among patients, has the potential to serve as an effective screening tool as well as therapeutic target. This study from the Yen lab identified a cancer-specific fusion gene called CDKN2D-WDFY2 that is present in 20% of HG-SC patients, by far the most frequent gene recombinant event found in this highly variable disease. Interestingly, the same fusion gene was also detected in an ovarian cancer cell line, further confirming its high occurrence.

The finding is important because this fusion gene could very well represent a major cellular lineage important for developing a better screening tool for detecting ovarian cancer.  Furthermore, the functions of parental genes that form the fusion gene are known to involve in cancer. One of the parental gene, CDKN2D, regulates cell-cycle and DNA repair. When these important functions go awry they can lead to cancer.  The other parental gene WDFY2 is known to modulate AKT, an important enzyme family known to play a role in cancer formation. If the aberrant fusion protein derived from the fusion gene is indeed involved in cancer formation, it could provide insight into the underlying mechanism of this deadly disease and used as a target for future therapies.

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