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  • 20260917-1
  • Lectures
  • Institute of Biomedical Sciences
  • Location

    B1B Lecture Room, IBMS

  • Speaker Name

    Dr. Wei-Ting Hung (NTU)

  • State

    Definitive

  • Url
The bottleneck to peritoneal metastasis varies across patients rather than cancer types

2026-09-17 11:00 - 12:00

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Metastasis is the leading cause of cancer-related mortality, yet our understanding of the metastatic process remains limited. Fundamental questions remain unanswered, such as whether all primary tumor cells possess metastatic potential and, if not, when and how certain cells acquire the ability to disseminate from the primary tumor. In this study, we aimed to quantify the metastatic bottleneck from a phylogenetic perspective across multiple cancer types, using peritoneal metastasis, a particularly devastating form of metastatic disease, as a model. We assembled a cohort of 32 patients with peritoneal metastases, including 12 pancreatic, 9 gastric, and 11 clear cell ovarian cancer cases. In addition, we incorporated a published cohort of colorectal cancer, resulting in a total of 56 phylogenetic trees containing peritoneal metastases. To quantify the bottleneck associated with peritoneal metastasis, we developed a novel metric, the Quintet Heterogeneity Index (QHI). QHI was first benchmarked using in silico simulations and subsequently applied to all phylogenies. Surprisingly, the degree of metastatic bottleneck was remarkably similar across the four cancer types. Both narrow and broad bottlenecks were observed in each cancer type, suggesting that the extent of the bottleneck is not cancer type-specific. Notably, in three cases exhibiting an extremely narrow bottleneck, peritoneal metastases clustered closely with lymph node metastases, indicating a potential evolutionary link between lymphatic dissemination and subsequent peritoneal spread. To investigate the molecular characteristics associated with the founders of peritoneal metastases, cases were classified into QHI-high and QHI-low groups. Somatic single-nucleotide variants (SNVs) and copy number alterations (CNAs) were identified using whole-exome sequencing. While the overall burden of SNVs was comparable between the two groups, the QHI-low group exhibited significantly higher levels of copy number alterations. Furthermore, odds ratio analysis identified loss of heterozygosity (LOH) on chromosome 9q as being strongly associated with the QHI-low group. By analyzing the phylogenies of 56 cancer cases with peritoneal metastases, this study demonstrates that cancer type is not the primary determinant of the metastatic bottleneck. Instead, the capacity to seed peritoneal metastases may be acquired either early or late during tumor evolution, and extensive copy number alterations may enhance the evolutionary fitness required for metastatic dissemination.