Abstract
Abstract Background: The extent to which metastatic tumors further evolve by accumulating additional mutations is unclear and has yet to be systematically addressed using next-generation sequencing in high-grade serous ovarian cancer. Methods: During cytoreductive surgery prior to chemotherapy, 11 spatially separated tumor samples from primary tumor and associated metastatic sites with 2 normal samples were obtained. Whole exome sequencing and copy number analysis were performed and multiplex PCR followed by ultra-deep resequencing was used for validation. Especially, omental samples were sequenced with high depth of coverage (∼200x).Phylogenetic tree was built to explore the evolutionary relationship between samples. Results: Only 6% of all somatic mutations were present in every sample of a given case with TP53 gene as the only known mutant gene consistently present in all samples. Two non-spatial clusters of primary samples (cluster 1 and 2), and a cluster of metastatic samples (cluster M) were identified. The patterns of mutations indicate that cluster M was originated from cluster 1, and that cluster 2 was diverged from a portion of right fimbriae in cluster 1 at the early phase of tumorigenesis. No significant metastatic sample-specific mutations or copy number changes were detected. Conclusion: Our results showed that high level of intratumor heterogeneity was evident in a high-grade serous ovarian cancer. Moreover, we showed that transcoelomic metastasis arises with little accumulation of somatic mutations or copy number alterations. Citation Format: Jung-Yun Lee, Jung-Ki Yoon, Duhee Bang, Yong-Sang Song. Identification of somatic mutations and copy number alterations in metastatic high-grade ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1547. doi:10.1158/1538-7445.AM2014-1547
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