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NIPT Platform Can Detect Copy Number Alterations in Some Gynecological Cancers

NEW YORK (GenomeWeb) – Platforms typically used for noninvasive prenatal testing could also be helpful to detect copy number alterations associated with gynecological cancers, according to a new study.

While noninvasive prenatal testing platforms have been developed to detect copy number alterations within fetal cell-free DNA from maternal plasma samples, researchers from the Showa University School of Medicine in Japan theorized that NIPT platforms could also capture CNAs in circulating cell-free DNA sloughed off by tumors and could represent a noninvasive, cost-effective way to detect cancer.

As they reported this week in Scientific Reports, the researchers were able to use such an approach to detect copy number alterations in about 20 percent of gynecological cancers they tested. The pipeline, they added, was better at detecting later-stage tumors, and samples in which the researchers could detect CNAs had poorer prognoses, suggesting that cancer CNAs detected in plasma could represent a prognostic biomarker.

"We focused on the application of CNA in plasma and believed that this method has a broader scope for genetic diagnoses, such as the analysis of [circulating tumor] DNA to detect cancer and predict prognosis, although its clinical utility must be further studied," Showa's Akihiko Sekizawa and his colleagues wrote in their paper.

The researchers enrolled 100 patients with gynecological cancers — 36 patients with ovarian cancer, 11 with cervical cancer, and 53 with endometrial cancer — in their study and collected plasma samples from them. Using GeneTech's NIPT platform, they detected CNAs in 19 samples.

In particular, the researchers used the SeqFF method to detect CNAs. In a NIPT setting, this approach relies on fragment length differences between fetal and maternal cell-free DNA to detect fetal CNAs. Here, the researchers counted on the hypothesis that circulating tumor DNA and cell-free DNA also differ in fragment length.

They were better able to detect CNAs in advanced-stage cancers, detecting CNAs in one of the 21 early-stage ovarian cancers, five of the 15 advanced-stage ovarian cancers, three of the 11 early-stage cervical cancers, five of the 41 early-stage endometrial cancers, and five of the 12 advanced stage endometrial cancers. The cohort had no patients with advanced-stage cervical cancer.

The overall detection rate for advanced cases was 37 percent, as compared to 12 percent for early-stage cases.

Through this approach, the researchers also could detect CNAs that affected particular genes. All the ovarian cancer cases with CNAs present, except one, had copy number losses of either BRCA1 or BRCA2, the researchers reported. Likewise, they uncovered CNAs affecting genes in the PI3k/Akt signaling pathway.

Additionally, endometrial cancer patients tended to have alterations affecting cancer driver genes like MYC and CCNE1.

A number of these affected genes, the researchers noted, are also drug targets.

Patients in whom the researchers uncovered CNAs had decreased progression-free and overall survival, as compared to those in whom CNAs were not found, so CNAs could serve as a prognostic cancer biomarker.

However, the researchers cautioned that their sample size was small and that they did not compare plasma DNA and tumor data to confirm the origins of the CNAs. Additionally, they said, prospective studies are needed to validate their method.

Still, they suggested that NIPT-type testing could eventually be used to noninvasively diagnose cancer as well as monitor recurrence and therapy response. "As sequencing techniques develop and become more affordable, noninvasive and longitudinal surveillance may become a valuable tool available to clinical oncologists," the researchers wrote.