Pheno-MYCN maps the morphological footprint of MYCN amplification in paediatric neuroblastoma

Authors

Chai, B., Fourkioti, O., Naidoo, R., De Vries, M., George, S., Chesler, L., Hutchinson, J. C., Bakal, C.

Abstract

MYCN amplification has long been a prognostic marker in paediatric neuroblastoma, yet is typically assayed in bulk, alongside rather than within the heterogeneous tissue architecture pathologists assess. This leaves a gap: MYCN status alone cannot localise MYCN-associated biology, while morphology alone cannot assign molecular risk. Motivated by our finding that the two together identify high-risk cases missed by either, we developed Pheno-MYCN, a weakly supervised framework linking slide-level MYCN prediction to interpretable morphological sub-populations on routine H&E whole-slide images. The aim is not a stronger classifier: prediction probes what MYCN amplification does to the tissue, its evidence open to pathological scrutiny. Across 189 slides, Pheno-MYCN resolved each into phenotypic clusters that expert review mapped to neuroblastoma morphologies. Cell-level profiling revealed MYCN amplification "marked" every sub-population, through a different feature in each: densely cellular yet disorganised tumour with sparser, less diverse networks; chiefly abundance in necrotic and haemorrhagic regions. MYCN-amplified-like tissue was identifiable per slide from these features alone (AUC 0.93-1.00, leave-one-slide-out) and traced as a continuous gradient within tumours. Thus MYCN amplification leaves a concrete, interpretable footprint that can be read and localised on routine H&E, offering a low-cost means to flag and map it where molecular testing is limited.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 22 Aug 2026.

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