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Across more than 20,000 tumour and normal samples, how much TROP2 a tissue makes was set mainly by chemical marks on its DNA rather than by mutations in its gene.
The authors integrated bulk and single-cell transcriptomes from more than 20,000 samples across TCGA, GTEx and public atlases to map TACSTD2 (TROP2) expression in solid tumours and healthy epithelia. Expression was restricted to epithelial lineages, enriched in several tumours and detectable in some normal epithelia. Genomic alterations of the gene were uncommon, whereas DNA methylation showed a consistent inverse association with expression, indicating dominant epigenetic control. TACSTD2 expression was linked to epithelial barrier programmes and variable immune interactions, and showed modest, context-dependent co-expression with genes involved in processing antibody-drug conjugates and in payload sensitivity. The authors conclude that antigen abundance alone is insufficient to predict ADC efficacy or toxicity.
If TROP2 levels are set by methylation rather than by mutation, a blood test that tracks a tumour's mutations carries almost no information about whether the cells left behind make TROP2. A test that reads methylation might.
Shares Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left, Naming which clone or phenotype is left after treatment, Sacituzumab govitecan, TROP2.
Shares Sacituzumab govitecan, TROP2, Triple-negative breast cancer (TNBC).
Shares Sacituzumab govitecan, TROP2.
Shares Datopotamab deruxtecan, Sacituzumab govitecan, TROP2, Triple-negative breast cancer (TNBC).
Shares Naming which clone or phenotype is left after treatment, TROP2, Triple-negative breast cancer (TNBC).
Shares Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left, Naming which clone or phenotype is left after treatment, DNA methylation profiling.
Shares TROP2, Breast cancer (all types).
Shares Sacituzumab govitecan, Breast cancer (all types), Triple-negative breast cancer (TNBC).
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