Spatial transcriptomics of retinoblastoma: a visual window on intra-patient heterogeneity

Area of Science:

• Ophthalmology
• Oncology
• Genomics

Background:

• Retinoblastoma is a common childhood eye cancer with variable differentiation and proliferation.
• Molecular subtypes (1 and 2) and intratumoral heterogeneity are known, but spatial mapping is lacking.
• Retinocytoma is a benign, non-proliferative tumor, posing diagnostic challenges.

Purpose of the Study:

• To map retinoblastoma cell populations spatially within a tumor.
• To correlate histological features with molecular subtypes.
• To investigate the diagnostic ambiguity between retinocytoma and retinoblastoma.

Main Methods:

• Spatial transcriptomics on a primary enucleated retinoblastoma with distinct histological areas.
• Analysis of whole transcriptomic profiles from 16 regions of interest.
• Immunohistochemistry for pathway markers and senescence markers.

Main Results:

• Transcriptomic clustering correlated with histological differentiation (highly vs. poorly differentiated).
• Subtypes 1 and 2 molecular signatures mapped perfectly to histological and transcriptomic profiles.
• Senescence marker analysis did not support a retinocytoma diagnosis in the differentiated area.

Conclusions:

• Strong correlation between histology and molecular profiling in retinoblastoma.
• First spatial mapping of adjacent retinoblastoma molecular subtypes 1 and 2.
• Need for specific biomarkers to differentiate retinocytoma from well-differentiated retinoblastoma (subtype 1).