# Pan-cancer multi-omic integration of Trop2 reveals biological determinants and translational implications for ADC therapy

Source: https://onco.cc/key-papers/paper-notini-trop2-pan-cancer-multiomic-npj-precis-oncol-2026/  
OnCo record `paper-notini-trop2-pan-cancer-multiomic-npj-precis-oncol-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: NPJ Precision Oncology
- Year: 2026
- DOI: 10.1038/s41698-026-01523-w
- Authors: Notini G, Galbardi B, Viale G, et al.
- Findings: More than 20,000 samples integrated across TCGA, GTEx and public atlases.; TACSTD2 genomic alterations were uncommon; DNA methylation was inversely associated with expression.; Antigen abundance alone did not predict ADC efficacy or toxicity.
- What it means: 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.
- Caveats: Associations in public expression data, not a clinical study.; Methylation was inversely associated with expression; whether it can be read from blood at useful levels is untested.

## Sources

- Notini et al., NPJ Precis Oncol 2026: https://doi.org/10.1038/s41698-026-01523-w
- PubMed: https://pubmed.ncbi.nlm.nih.gov/42297906/

## Connected records

- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- fronts: [Antibody-Drug Conjugates](https://onco.cc/fronts/adcs/)
- technologies: [DNA methylation profiling](https://onco.cc/technologies/methylation-profiling/)
- targets: [TROP2](https://onco.cc/targets/trop2/)
- drugs: [Datopotamab deruxtecan](https://onco.cc/drugs/datopotamab-deruxtecan/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/)
- bottlenecks: [Naming which clone or phenotype is left after treatment](https://onco.cc/bottlenecks/b-subclone-attribution-residual-disease/)
- ideas: [Read methylation and mutation on the same cell-free DNA fragment to tell what kind of cancer is left](https://onco.cc/ideas/idea-same-fragment-methylation-and-mutation/)

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