Abstract 710: Exosomal DNA has the potential to detect circulating tumor DNA in patients with colorectal cancer

[Introduction] Exosomes are small vesicles of endosomal origin, which are released by all cell types, and are involved in physiological and pathological processes including cancer progression and metastasis. Exosomes comprise proteins, lipids, and nucleic acids such as RNA and DNA (exoDNA). Circulating exoDNAs harboring mutations are detected in patients with pancreatic or colorectal cancer. [Objective] To evaluate the clinical utility of detecting RAS mutations in exoDNAs of patients with colorectal cancers. [Methods] We prospectively recruited 25 patients with RAS mutations in cells of their colorectal tissues. Circulating exoDNA was extracted from exosomes in 1 ml of preoperative plasma. Circulating cell-free DNA (ccfDNA) was concurrently extracted from 1 ml of plasma. We identified RAS mutations in exoDNAs and ccfDNAs using droplet digital PCR (ddPCR, Biorad). [Results] We analyzed the exoDNAs of patients with right-sided (n = 13) and left-sided (n = 12) colon cancers (Stage II, [n = 9]; Stage III, [n = 9], Stage IV, [n = 7]). The median concentrations of exoDNA and ccfDNA were 52.3 ng/ml (32.1-223 ng/ml) and 132 ng/ml (41.3-4333 ng/ml). RAS mutations were detected in exoDNAs of 13 patients (52.0%) and in the ccfDNAs of 5 patients (20%) (P=0.03). The sensitivities of exoDNAs and ccfDNAs were equivalent (57.1%). However, for Stages II and III, the sensitivities of exoDNAs were higher compared with those of ccfDNAs. Notably, the sensitivity of exoDNA of Stage III was 77.8%. RAS mutations were undetectable in ccfDNAs of patients without detectable mutations in exoDNAs. The median mutation allele frequencies of exoDNA and ccfDNAs were 12.1% and 18.0%, respectively. [Conclusion] Previously reported mutation-detection rates using Stages VI and III ccfDNAs are 90% and 15%, respectively. Here, the sensitivities using ccfDNAs for Stage II or III were low as well. Conversely, the sensitivities using exoDNAs were equivalently high in Stages III and Stage IV. These findings indicate that exoDNA has superior potential for detecting circulating tumor DNA compared with that of ccfDNA Citation Format: Sho Kuriyama, Takeshi Yamada, Michihiro Koizumi, Seiichi Shinji, Akihisa Matsuda, Ryo Ohta, Goro Takahashi, Masahiro Hotta, Keisuke Hara, Kohki Takeda, Koji Ueda, Hiroshi Yoshida. Exosomal DNA has the potential to detect circulating tumor DNA in patients with colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 710.