Copy number variation of circulating tumor DNA detected using NIPT in neoadjuvant chemotherapy treated ovarian cancer patients

Analysis of circulating tumor DNA (ctDNA) can be used to characterize and monitor cancers. Recently, non-invasive prenatal testing (NIPT) as a new next-generation sequencing (NGS)-based approach applied to detecting ctDNA. This study aimed to investigate the copy number variations (CNVs) utilizing the NIPT in plasma ctDNA from ovarian cancer (OC) patients who were treated with neoadjuvant chemotherapy (NAC). The plasma samples of six patients, including stage II-IV, were collected at the pre-and post NAC treatment that divided into NAC sensitive and NAC resistant groups during the follow-up time. CNV analysis was performed using the NIPT via two methods” an open-source algorithm WISECONDORX and NextGENe software”. Results of these methods were compared in pre-and post-NAC of OC patients. WISECONDORX analysis indicated fewer CNV changes on chromosomes before treatment in the NAC sensitive rather than NAC-resistant patients. NextGENe data indicated that CNVs are not only observed in the coding genes, but also in non-coding genes. CNV in six genes was identified, including HSF1, TMEM249, MROH1, GSTT2B, ABR, and NOMO2, only in NAC-resistant patients. Bioinformatics analysis reveals the highest incidence of CNV in MROH1, TMEM249, and HSF1 genes on chromosome (Chr) 8. Chr8 study using WISECONDORX revealed CNV modifications in NAC-resistant patients prior to NAC therapy, but no CNV changes in NAC-sensitive individuals. Our findings showed low coverage whole genome sequencing analysis used for NIPT could identify CNVs in ctDNA of OC patients before and after chemotherapy. These CNVs are different in NAC-sensitive and resistant patients highlighting the potential application of this approach in cancer patient management.