Liquid biopsies predict ovarian cancer recurrence

By Liz Meszaros, MDLinx
Published July 27, 2016

Key Takeaways

Researchers at the Mayo Clinic may have found a way—through liquid biopsies based on blood testing and DNA sequencing—to effectively detect ovarian cancer recurrence even before a tumor recurs, according to their study results published in the journal Scientific Reports.

This is good news in the battle against ovarian cancer, which is one of the most deadly cancers because tumors often go undetected until the late stages are reached, and recur approximately in approximately 75% of women. In 2015, over 14,000 women died of ovarian cancer in the United States, while over 21,000 were newly diagnosed.

“With liquid biopsies, we don’t have to wait for tumor growth to get a DNA sample,” said senior author George Vasmatzis, PhD, department of laboratory medicine and pathology, Mayo Clinic, Rochester, MN. “This important discovery makes it possible for us to detect recurrence of the disease earlier than other diagnostic methods. We can repeat liquid biopsies to monitor the progression of the cancer. That gives hope of a better treatment plan over time.”

Dr. Vasmatzis and fellow researchers selected 10 of 100 consecutive patients with suspected epithelial serous stage IIIC-IV ovarian cancer who had been seen at the Mayo Clinic between August 1, 2010, and April 30, 2012. They chose late-stage ovarian cancer patients due to their higher tumor burden and therefore, higher circulating tumor DNA (ctDNA) content.

From these 10 subjects, blood was obtained before and after surgery, and their primary tumors were assessed by a pathologist for tumor purity of at least 60%. Researchers then isolated and analyzed DNA for structural variations, and measured CA-125 within 20 days of the associated cell-free DNA (cfDNA) blood draw. CfDNA was isolated from 3 ml of double-spun plasma, and quantification of total cfDNA was done using the Quant-iT PicoGreen dsDNA reagent. As a negative control, researchers also pooled and processed 3 ml of plasma or serum from patients without cancer.

“In this study, the blood drawn before and after surgery and the surgical tissue were used to identify DNA fragments with abnormal junctions that can only be seen in this patient’s tumor DNA,” explained Dr. Vasmatzis.

Patients in whom the post-surgical DNA did not match tumor DNA were found to be in remission, and conversely, those in whom post-surgery DNA matched the DNA of the tumor, recurrence of ovarian cancer was seen.

“Next-generation mate-pair sequencing was used to identify specific DNA changes of the tumor to create an individualized monitoring panel for liquid biopsy. This allows us to shape treatment to the individual patient rather than using a standard treatment that may not work for everyone,” he concluded.

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