ArticleExperimental & molecular medicine2023
Metastatic pattern of ovarian cancer delineated by tracing the evolution of mitochondrial DNA mutations.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 11 citations in OpenAlex.
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- Spectrum and Impact of Mitochondrial DNA Mutations in Ovarian Cancer.International journal of molecular sciences · 2025Review
- Unlocking the mitochondrial functional code: unraveling the pathogenesis of ovarian cancer and innovative targets to inhibit malignant behavior.Journal of translational medicine · 2025Review
- Carcinoma-associated mesenchymal stem cells promote ovarian cancer heterogeneity and metastasis through mitochondrial transfer.Cell reports · 2024Article
- Comparison of capture-based mtDNA sequencing performance between MGI and illumina sequencing platforms in various sample types.BMC genomics · 2024Article
- Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer-specific evolutionary pattern contributing to high oxidative metabolism.Clinical and translational medicine · 2024Article
- Research Progress of Traditional Chinese Medicine Monomer Inhibiting Metastatic Colonization of Ovarian Cancer Cells Based on Cell Biology.Integrative cancer therapiesReview
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
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Abstract
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. An increasing number of studies have leveraged mitochondrial DNA (mtDNA) mutations as efficient lineage-tracing markers of tumor clonality. We applied multiregional sampling and high-depth 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. 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. Our study presents an explicit view of the OC metastatic pattern, which sheds light on efficient treatment for OC patients.
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