Mutational landscape and evolutionary pattern of peritoneal metastases in colorectal cancer.

• DOI: 10.1200/jco.2024.42.16_suppl.e15533
• Publication Date: 2024-06-21T19:31:40Z
• Authors: Yuzhuo Wang; Xianfeng Xu; Jinyu Zheng; Lu Xu; Yuping Zhu; Rui Xu; Yan Shen; Guifang Xu; Weiyou Zhu; Zan Fu; Jing Sun
• Keywords: 03 medical and health sciences; 0302 clinical medicine

e15533 Background: Peritoneal metastases occur in approximately 10% of all colorectal cancer (CRC) patients, which are associated with significant morbidity and worse clinical outcome. To date, the evolutionary pattern molecular mechanisms peritoneal remains largely unknown, provided little insights into prevention treatment this subgroup CRC patients. Methods: We performed whole-exome sequencing (WES) on 49 samples matched primary tumors, metastases, lymph node from 11 Phylogenetic reconstruction analyses were to investigate mode route metastatic dissemination. The timing dissemination was inferred using SCIMET. Metastases-associated driver events analyzed validated two independent cohorts. Finally, therapeutic actionability somatic alterations assessed. Results: A characterization found that 3 out patients displayed monoclonal Whereas other 8 exhibited polyclonal dissemination, 6 monophyletic 2 polyphyletic. In five we observed evidence for metastasis-seeding-metastasis among metastases. Additionally, mainly seeded by tumor rather than Metastatic inference most (9 11) occurred early before became clinically detectable. Genetic identified, including mutations TP53, SMAD4, KRAS, RNF43, SMARCB1, as well focal amplifications (8p24) losses (17p12). Analysis identified potentially targetable oncogenic Conclusions: Our results important features had profound implications prediction, prevention, metastasis CRC.