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Genetic Similarities Identified in Primary and Metastatic Ovarian Tumors

By: Cordi Craig
Posted: Monday, January 21, 2019

Early metastases and resistance to chemotherapy have led to low survival rates and a poor prognosis among patients with ovarian cancer. However, results from a genetic mutational study, reported in the Proceedings of the National Academy of Science, may suggest potential molecular targets of the disease as well as opportunities for personalized treatment. Alessandro D. Santin, MD, and colleagues, of the Yale School of Medicine, New Haven, Connecticut, identified genetic similarities in primary, metastatic, and recurrent ovarian tumors—potential explanations for unsuccessful early detection.

Using whole-exome sequencing, the authors evaluated ovarian tumors (64 primary, 41 metastatic, and 17 recurrent) among 77 patients, along with matched normal DNA. To evaluate their evolutionary history, the authors sequenced 13 pairs of synchronous bilateral ovarian cancer. Lastly, they studied the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 in primary tumors and xenografts with c-MYC amplifications.

Genetic similarities between primary and metastatic ovarian tumors suggested that transcoelomic metastases occur early in the development of ovarian cancer. Furthermore, the synchronous bilateral ovarian cancer sequencing revealed that ovarian tumors share a common ancestor before evolving independently.

Among the 17 patients with matched tumors, 4 gained PIK3CA amplifications and 2 gained c-MYC amplifications in the recurrent tumors and showed no loss of amplification or gain of deletions. In preclinical experiments, the authors found that c-MYC–amplified chemotherapy-resistant cell lines and xenografts were sensitive to JQ1 and GS-626510 (P = .01), suggesting that oral BET inhibitors may prove to be an effective targeted therapy.

Disclosure: The study authors reported no conflicts of interest.



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