Abstract 129: Determine the genetic similarity of synchronous endometrial and ovarian cancers with variants in polyguanine sequences
Authors: Huang Yu-Yi , Cheng Pei-Chi , Hsu Ching , Jeng Yung-Ming , Wei Lin-Hung , Hung Wei-Ting 
Published: April 2023

Endometrial and ovarian cancers are both fearsome gynecological diseases with high mortality rates worldwide. Due to their histological similarity, it is still a clinical challenge to distinguish between double primary cancer (DPC) and metastasis cancer (MC) in synchronous endometrial and ovarian cancers in which the latter represents a poor prognostic outcome. Clinically, the standard procedure for examining DPC and MC relies on their morphology and histopathology; however, showing poor accuracy even under explicating criteria. Here, we attempt to utilize indel variants within polyguanine (polyG) sequences to generate genetic distances of synchronous endometrial and ovarian tumors to normal tissue in a patient and then calculate the correlation coefficient for them. Polyguanine sequences are hypermutable guanine repeats that acquire insertion or deletion at a high incident rate (mutation rate: ~10-6 - 10-4; ~1000 folds higher than unique sequence) and, therefore, could serve as a very rich resource for comparing the genetic similarity between samples. The correlation between selected clinical variables, e.g., disease-free survival and the described correlation coefficient is then calculated to test whether this protocol can serve as an optimal tool for distinguishing between DPC and MC. We have assembled a cohort of 39 patients with synchronous endometrial and ovarian cancers in which pathologists cannot determine the relationship between endometrial and ovarian cancer in 23 of them. Preliminarily, we have collected DNA from formalin-fixed paraffin-embedded (FFPE) specimens and completed polyG genotyping for four of them. Indel variants, both insertions and deletions, are rich in all cases indicating the approach is technically rigid for this purpose even with FFPE specimens. Subsequently, we evaluate the similarity between endometrial and ovarian cancer by calculating Spearman's correlation with the genetic distances obtained from polyG genotyping. As the result of preliminary cases, we observe the correlation coefficient spreading between -0.14 to 0.95, implying this methodology can determine the genetic similarity between endometrial and ovarian tumor in a case and, therefore, could be a potential tool to supplement the current observation-based approach in the clinic. Our next step is to correlate the correlation coefficients with meaningful clinical variables once we complete genotyping the entire cohort. We anticipate this approach could provide additional information to distinguish DPC and MC and therefore benefit the patients.

Citation Format: Yu-Yi Huang, Pei-Chi Cheng, Ching Hsu, Yung-Ming Jeng, Lin-Hung Wei, Wei-Ting Hung. Determine the genetic similarity of synchronous endometrial and ovarian cancers with variants in polyguanine sequences [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 129.