RT Journal Article SR Electronic T1 PR065/#611  Metastatic pattern of ovarian cancer delineated by tracing the evolution of mitochondrial DNA mutations JF International Journal of Gynecologic Cancer JO Int J Gynecol Cancer FD BMJ Publishing Group Ltd SP A67 OP A67 DO 10.1136/ijgc-2023-IGCS.105 VO 33 IS Suppl 4 A1 Xu, Zhiyang A1 Wang, Xingguo A1 Liu, Shujuan YR 2023 UL http://ijgc.bmj.com/content/33/Suppl_4/A67.abstract AB Introduction Ovarian cancer (OC) is the most lethal gynecologic tumor and is characterized by a high rate of metastasis. Challenges in accurately delineating the metastatic pattern have greatly restricted the improvement of treatment in OC patients.Methods We applied multiregional sampling and high-depth mitochondrial DNA (mtDNA) sequencing to determine the metastatic patterns in advanced-stage OC patients. Somatic mtDNA mutations were profiled from a total of 195 primary and 200 metastatic tumor tissue samples from 35 OC patients.Results Our results revealed remarkable sample-level and patient-level heterogeneity. In addition, distinct mtDNA mutational patterns were observed between primary and metastatic OC tissues. Further analysis identified the different mutational spectra between shared and private mutations among primary and metastatic OC tissues. Analysis of the clonality index calculated based on mtDNA mutations supported a monoclonal tumor origin in 14 of 16 patients with bilateral ovarian cancers. Notably, mtDNA-based spatial phylogenetic analysis revealed distinct patterns of OC metastasis, in which a linear metastatic pattern exhibited a low degree of mtDNA mutation heterogeneity and a short evolutionary distance, whereas a parallel metastatic pattern showed the opposite trend. Moreover, a mtDNA-based tumor evolutionary score (MTEs) related to different metastatic patterns was defined. Our data showed that patients with different MTESs responded differently to combined debulking surgery and chemotherapy. Finally, we observed that tumor-derived mtDNA mutations were more likely to be detected in ascitic fluid than in plasma samples.Conclusion/Implications Our study presents an explicit view of the OC metastatic pattern.