Single-cell analysis identifies aggressive cell states in some rhabdomyosarcomas

Researchers compared rhabdomyosarcoma samples from 16 children: four with fusion-negative tumors that proved fatal, four with fusion-positive tumors, and eight with fusion-negative disease who remained alive. They used single-cell RNA sequencing and spatial transcriptomics to examine gene activity within cells and its location in tumor tissue, looking for features not captured by conventional risk classification.

Some fusion-negative tumors contained cell populations with gene-activity patterns resembling those in fusion-positive, high-risk tumors. The researchers also identified different genetic changes that appeared to affect overlapping cellular pathways, suggesting that tumors may reach a similar aggressive state through distinct genetic routes.

The findings may help explain why some children whose tumors lack the established genetic warning sign nevertheless have poor outcomes. However, this was a small, exploratory analysis and does not establish a test that predicts outcomes or show that changing treatment improves survival. The researchers are expanding the work to hundreds of samples; the proposed use of biological signatures to refine risk assessment, and potential therapies such as CAR-T, remains under investigation.