Single-cell analysis of tumours from 16 children suggests some rhabdomyosarcomas without the usual high-risk genetic marker still carry aggressive cell populations, which could sharpen risk prediction.
Scientists from the Wellcome Sanger Institute, the University of Cambridge, Great Ormond Street Hospital (GOSH), University College London and collaborating institutions report that some childhood tumours classed as lower risk contain hidden, highly aggressive cancer cells. The work, published in Cancer Research, focuses on rhabdomyosarcoma (RMS), an aggressive cancer of muscle tissue that is among the most common soft-tissue cancers in children under 15; about 55 children are diagnosed with it in the UK each year. Doctors traditionally split RMS by whether a tumour carries a gene fusion linked to especially aggressive disease, yet some children whose tumours lack that marker still die, and the reason has been unclear.
To investigate, the team examined tumour samples from 16 children: four with fusion-negative cancers that proved fatal, four with fusion-positive tumours, and eight with fusion-negative disease who survived. They used single-cell RNA sequencing, which measures gene activity in individual cells, and spatial transcriptomics, which maps that activity within the tumour. Some tumours classed as non-high-risk contained cells whose gene-activity patterns closely resembled those in high-risk tumours, and rare genetic changes in these tumours affected many of the same cellular pathways. The researchers interpret this as different genetic routes converging on a shared aggressive cell state.
The authors say this could change how risk is judged: identifying the biological signature of aggressive cells at diagnosis might flag children at greater risk of relapse even when standard genetic tests look reassuring, while sparing children with truly lower-risk disease some intensive chemotherapy. Immunotherapies such as CAR-T cell therapy are mentioned as a possible future direction, but they would need substantial further development and testing for RMS. The team is now extending the work to hundreds more tumour samples, so the findings, drawn from a small group of 16 children, remain early-stage research rather than a change to current clinical practice.
