Comparison of Somatic Mutation Profiles Between Formalin-Fixed Paraffin Embedded Tissues and Plasma Cell-Free DNA from Ovarian Cancer Patients Before and After Surgery

Abstract

Ovarian carcinogenesis can be induced by a large number of somatic gene mutations. Circulating tumor DNA (ctDNA) released into peripheral blood can provide insights into the genomic landscape of cancer cells and monitor their dynamics. Our aim was to detect and compare the genetic profiles in tumor tissue and plasma before and after tumor resection in ovarian cancer patients. All three samples were collected from each patient. In this study, we used a commercial cancer panel to identify somatic mutations in 26 genes in seven selected patients through next-generation sequencing on the Illumina platform. Overall, 16 variants with pathogenic effect were identified in the TP53, PIK3CA, PTEN, APC, NRAS, KRAS, GNAS, and MET genes involved in important signaling pathways. The genetic alterations found in the presurgical plasma in six of seven ovarian cancer patients were no longer present in the plasma after tumor surgical removal. Identical variants in formalin-fixed paraffin embedded (FFPE) tissues and preoperative plasma specimens were observed in only two cases. These findings suggest that the detected presurgical pathogenic variants absent in postsurgery plasma are associated with the primary ovarian tumor. Finally, the low-identified concordance between FFPE and plasma can be due to various factors, but most likely to high tumor heterogeneity and low ctDNA level.

Mutation analysis of circulating tumor DNA and paired ascites and tumor tissues in ovarian cancer

“…ctDNA has exhibited a considerable clinical value as a tumor biomarker in diagnosis and disease monitoring of ovarian cancer ( 27 ). However, few studies compared the sequencing results of ctDNA, paired ascites and tumor tissue samples in ovarian cancer ( 28 , 29 ). A parallel analysis of these three types of samples mainly explained the potential of ascites and ctDNA to reflect the mutational landscape in 10 patients ( 30 ), although these results require further validation.…”