ArticleGenome medicine2021
Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
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- Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotype and phenotype in chronic lymphocytic leukemia.bioRxiv : the preprint server for biology · 2024Article
- quickBAM: a parallelized BAM file access API for high-throughput sequence analysis informatics.Bioinformatics (Oxford, England) · 2023Article
- A transcriptome-informed QSP model of metastatic triple-negative breast cancer identifies predictive biomarkers for PD-1 inhibition.Science advances · 2023Article
- Targeting interleukin-13 receptor α2 (IL-13Rα2) for glioblastoma therapy with surface functionalized nanocarriers.Drug delivery · 2022Review
- Review
- Novel temporal and spatial patterns of metastatic colonization from breast cancer rapid-autopsy tumor biopsies.Genome medicine · 2021Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMetastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood.
methodsVia rapid autopsy, we have collected 30 tumor samples over 3 timepoints and across 8 organs from a triple-negative metastatic breast cancer patient. The large number of sites sampled, together with deep whole-genome sequencing and advanced computational analysis, allowed us to comprehensively reconstruct the tumor's evolution at subclonal resolution.
resultsThe most unique, previously unreported aspect of the tumor's evolution that we observed in this patient was the presence of "subclone incubators," defined as metastatic sites where substantial tumor evolution occurs before colonization of additional sites and organs by subclones that initially evolved at the incubator site. Overall, we identified four discrete waves of metastatic expansions, each of which resulted in a number of new, genetically similar metastasis sites that also enriched for particular organs (e.g., abdominal vs bone and brain). The lung played a critical role in facilitating metastatic spread in this patient: the lung was the first site of metastatic escape from the primary breast lesion, subclones at this site were likely the source of all four subsequent metastatic waves, and multiple sites in the lung acted as subclone incubators. Finally, functional annotation revealed that many known drivers or metastasis-promoting tumor mutations in this patient were shared by some, but not all metastatic sites, highlighting the need for more comprehensive surveys of a patient's metastases for effective clinical intervention.
conclusionsOur analysis revealed the presence of substantial tumor evolution at metastatic incubator sites in a patient, with potentially important clinical implications. Our study demonstrated that sampling of a large number of metastatic sites affords unprecedented detail for studying metastatic evolution.
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