Scientists Reveal Why Some Childhood Tumours Become Aggressive

Some childhood cancers that appear less dangerous during diagnosis may secretly contain highly aggressive cancer cells, according to a new study. Researchers have discovered that certain tumours lacking conventional high-risk genetic markers can still behave like the most aggressive forms of cancer, potentially explaining why some children experience poor outcomes despite apparently favourable risk classifications.

Published in the journal Cancer Research, the study conducted by researchers from the Wellcome Sanger Institute, University of Cambridge, Great Ormond Street Hospital and collaborating institutions investigated the biology of rhabdomyosarcoma, a rare but aggressive childhood cancer that develops from muscle-related tissues.

Doctors commonly classify rhabdomyosarcoma according to the presence or absence of specific gene fusions associated with aggressive disease.

However, some children whose tumours lack these genetic abnormalities still develop life-threatening cancers.

To investigate this, researchers analysed tumour samples from 16 children, including four with fatal fusion-negative disease, four with fusion-positive tumours and eight survivors with fusion-negative disease.

Using single-cell RNA sequencing and spatial transcriptomics, researchers examined gene activity in individual cancer cells and mapped their distribution within tumours.

The findings revealed that some supposedly lower-risk tumours contained hidden populations of aggressive cancer cells displaying molecular characteristics similar to those found in high-risk disease.

Importantly, researchers discovered that different genetic abnormalities could activate similar biological pathways, producing aggressive cancer behaviour even without the usual high-risk gene fusion.

This suggests that tumour aggressiveness may depend not only on specific mutations but also on the biological state of cancer cells.

Researchers believe identifying these aggressive cellular signatures could eventually improve risk assessment and help doctors select more appropriate treatments.

The discovery could also support the development of targeted therapies, including potential immunotherapy approaches.

However, the study involved a small number of tumour samples, and the findings require validation in larger patient groups.

REFERENCE: Holly J. Whitfield, et al.; High-Risk Rhabdomyosarcomas Feature a Convergent Cell State. Cancer Research, 2026; 86 (19): 4991 DOI: 10.1158/0008-5472.CAN-25-4403