Whole-Exome Sequencing Reveals Clinical Potential of Circulating Tumor DNA from Peritoneal Fluid and Plasma in Endometrial Cancer

• Published in: Cancers 2022-05, Vol.14 (10), p.2506
• Main Authors: Ju, Hye-Yeon, Ho, Jung Yoon, Kang, Jun, Hur, Soo Young, Kim, Sejin, Choi, Youn Jin, Han, Mi-Ryung
• Format: Article
• Language: English
• Subjects: Algorithms; Biomarkers; Biopsy; Cancer; Cellular biology; Copy number; Cytology; Deoxyribonucleic acid; DNA; Endometrial cancer; Endometrium; Genes; Genomes; Immunohistochemistry; Microsatellite instability; Mutation; p53 Protein; Patients; Peritoneal fluid; Peritoneum; Plasma; PTEN protein; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14102506

Endometrial cancer (EC) is the most common type of gynecological cancer. Studies comparing tumor gDNA and ctDNA isolated from the plasma and peritoneal fluid of EC patients are limited. Whole-exome sequencing and P53 immunohistochemistry of 24 paired tissue, plasma, and peritoneal fluid samples from 10 EC patients were performed to analyze somatic mutations, copy number alterations, microsatellite instability, and mutational signatures. Mutations in cancer-related genes ( , , , , and ) and genes related to EC ( , , , and ) were identified with high frequencies among the three samples. and mutations, which are highly related to the molecular classification of EC, were identified based on several key observations. The ctDNA of two patients with negative peritoneal fluid presented mutations concordant with those in tissues. ctDNA from the plasma and peritoneal fluid of a patient with positive cytology harbored both and mutations, although none were detected in tissues. Additionally, the patient presented with wild type P53 immunohistochemistry, with a focal "high" expression in a "low" wild type background. The tissues and peritoneal fluid of 75% EC patients showed concordant microsatellite instability. Furthermore, we observed strong mutational concordance between the peritoneal fluid and tumors. Our data suggest that the ctDNA from peritoneal fluid might be a suitable biomarker for identifying the mutational landscape of EC and could complement tumor heterogeneity.