Good news! Cancer is history (soon)!
"New insights into why some children with rhabdomyosarcoma (RMS) develop aggressive disease despite being classified as non-high-risk have been uncovered. ...
RMS is broadly split into two different types, depending on whether the tumour contains a genetic risk marker. This marker is a fusion of two genes that are not normally connected. In patients with this marker, survival is substantially lower than in those who do not carry it, despite intense treatment.2
However, some children whose tumours do not carry the high-risk marker still develop aggressive disease, and it is unclear why this happens.
In a new study, researchers ... sought to understand why this group of non-high-risk patients go on to experience such an aggressive cancer. ...
In particular, they used single-cell RNA sequencing, which is a technique that allowed the team to examine gene activity in individual cancer cells. This revealed the true aggressive face of cancer cells that had ordinarily been classified as non-high-risk.
The team also used a method called spatial transcriptomics, which enabled the scientists to map where the cancer cells were located within the tumour, revealing how aggressive cell populations are organised within the cancer tissue.
The study revealed that aggressive tumours of children who had been classified as non-high-risk have gene expression patterns that closely resemble those of high-risk tumours, despite lacking the genetic risk marker.
They also found that children with non-high-risk tumours which behaved aggressively carry rare genetic changes that affect the same cellular pathway as high-risk tumours. This suggests that there are multiple genetic routes leading to the same aggressive tumours. ..."
From the abstract:
"Somatic mutations often predict survival in childhood cancers, as exemplified in rhabdomyosarcoma (RMS), in which FOXO1 gene fusion status is a key prognostic feature.
In this study, we examined single-cell transcriptomes and discovered that cancer cells of lethal disease converge on a common cell state with a shared transcriptional landscape, irrespective of fusion status.
Nuclear transcriptomics, chromatin accessibility, spatial transcriptomics, perturbation studies, and previously published datasets validated the overarching high-risk cell state.
The convergent cell state only partially overlapped with transcriptional effects of the FOXO1 fusion and unexpectedly exhibited neural features.
Overall, these findings delineate a cell state of high-risk RMS cells that transcends conventional molecular and histologic boundaries, suggesting an overarching disease phenotype that could transform target discovery and inform clinical practice."
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