'Lower-Risk' Childhood Cancer May Hide Aggressive Cells, Study Finds

Researchers have found that some children with rhabdomyosarcoma (RMS), a childhood cancer that develops from muscle tissue, may have aggressive cancer cells hidden inside tumours that doctors currently classify as lower-risk. RMS is among the most common soft-tissue cancers in children under 15, with about 55 cases diagnosed each year in the UK. The findings, from the Wellcome Sanger Institute, the University of Cambridge, Great Ormond Street Hospital and University College London, were published in the journal Cancer Research.

RMS is usually split into two groups based on whether a tumour carries a genetic marker formed when two normally separate genes fuse together; children with this fusion have substantially poorer survival even with intensive treatment. But some children whose tumours lack the marker still go on to develop aggressive disease, and doctors have not understood why.

Using single-cell RNA sequencing, which measures gene activity in individual cells rather than averaging across a whole tumour, and spatial transcriptomics, which tracks where those cells sit within the tissue, the researchers found aggressive cancer cells hidden inside tumours that conventional classification had labelled non-high-risk. These aggressive cells showed patterns of gene activity closely resembling those in high-risk tumours, even without the genetic fusion marker, and the researchers also found rare genetic alterations in these tumours that disrupted the same cellular pathways as high-risk disease.

"By studying tumours one cell at a time, we uncovered hidden populations of aggressive cancer cells that conventional methods miss," said Dr. Karin Straathof of the UCL Cancer Institute and Great Ormond Street Hospital, a co-senior author of the study. "Although these tumours carry different genetic changes, many converge on the same aggressive pathways." The researchers are now expanding their analysis to hundreds of additional tumour samples to look for more of the rare genetic routes that can produce aggressive childhood cancer.