Related Experiment Video
Updated: Sep 23, 2026
Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
Multi-site sequencing supports dual-track evolution and identifies candidate metastasis-associated factors in gastric
Peiyu Zhu1, Xiaofang Xing2, Ke Ji1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China.
Background:
Gastric cancer ovarian metastasis (GCOM) is an aggressive clinical entity whose evolutionary dissemination routes and molecular features remain incompletely defined.
Methods:
We performed whole-exome sequencing and patient-level phylogenetic reconstruction of 81 spatially distinct tumour specimens from 17 patients with GCOM.
Results:
Ovarian metastases showed a higher tumour mutational burden than matched primary tumours and substantial inter-lesional genomic heterogeneity. Phylogenetic reconstruction supported two major evolutionary routes of ovarian dissemination: lymph node-dependent evolution, in which ovarian metastases were phylogenetically associated with lymph node-related lineages, and lymph node-independent evolution, in which ovarian and lymph node metastases diverged along separate branches. Putative driver-gene alterations were relatively enriched in the shared/truncal mutational fraction, and SCAF4 emerged as an understudied candidate metastasis-associated factor. In GC cells, SCAF4 depletion was accompanied by widespread alterations in RNA splicing and interferon-related transcriptional programs and enhanced proliferative, migratory, invasive, and clonogenic phenotypes.
Conclusions:
These findings support a dual-route evolutionary framework for GCOM and nominate SCAF4 as a candidate metastasis-associated factor, providing a genomic basis for understanding the biological heterogeneity of ovarian dissemination in GC.
Highlights:
A multi-site genomic sequencing and phylogenetic reconstruction in matched gastric primaries and ovarian metastases was performed. Uncovered two distinct evolutionary routes for gastric cancer ovarian metastasis: lymph node-dependent and lymph node-independent evolutionary patterns. Genomic and functional analyses nominate SCAF4 as a candidate metastasis-associated factor.
