Abstract 771P
Background
Borderline ovarian tumors (BOT) are ovarian lesions with lower malignant potential compared to ovarian cancer (OV). The prognosis of patients with BOT is generally good but a small proportion of BOT can grow into OV. It remains unclear what the molecular characteristics of BOT are and how they may develop into OV.
Methods
We collected matched BOT and OV samples from 20 OV patients together with normal tissues and performed whole-exome sequencing (WES) on these samples. We conducted a comprehensive bioinformatics analysis to reveal the molecular features that distinguish BOT from OV and elucidate their evolutionary relationships.
Results
Among 37 known ovarian cancer driver genes, we detected 30 in at least one patient in this cohort, including ERBB2 (35%) and KMT2D (35%) as the most frequently mutated genes. We find that compared with BOT, OV shows relatively higher tumor mutation burden (paired Wilcoxon rank sum test, p = 0.059), but similar microsatellite instability (paired Wilcoxon rank sum test, p = 0.74). Although only 2 out of 20 (10%) patients with loss-of-function somatic mutations in BRCA1/2, we detected Signature 6 (defective DNA mismatch repair) in both BOT and OV. Interestingly, we only detected Signature 10 in OV, which implies the role of POLE defects contributing to high TMB in OV. Although BOT and matched OV may have the same initiating events, we note that the two ovarian lesions from 11 out 20 (55%) patients do not share any well-known driver event.
Conclusions
Based on the molecular profiling of BOT and OV samples from the same patients, we observed the frequency of DNA mismatch repair defect in OV patients and identify the significant contributions of POLE in tumorigenesis. The two matched lesions from some of ovarian patients show no shared driver events, implying independent origin.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
M. Wu.
Funding
Has not received any funding.
Disclosure
Y. Zhao, X. Peng, T. Li, H. Li: Financial Interests, Institutional, Full or part-time Employment: Presicions Scientific (Beijing) Co., Ltd. All other authors have declared no conflicts of interest.