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Researchers uncover what drives aggressive bone cancer

New research has identified a novel mechanism driving osteosarcoma – an aggressive paediatric bone cancer – providing insights to help predict patient outcomes and improve the condition’s management.

The study, published in Cell, used data from the 100,000 Genomes Project and is a collaboration between Genomics England, EMBL’s European Bioinformatics Institute, University College London (UCL), the Royal National Orthopaedic Hospital (RNOH).

Although osteosarcoma is a rare form of cancer, it has a significant impact on young people and their families as treatment can require surgery or amputation. The cancer also has the potential to spread to other organs, most commonly the lungs. Because osteosarcoma is so genomically complex, it has been challenging so far to identify what DNA changes in cells drive the cancer and consequently make significant advances in treatment options.

The research analysed whole-genome data from patients with osteosarcoma and identified a new type of genetic change, called loss-translocation-amplification (LTA) chromothripsis, which is present in around half of high-grade osteosarcoma cases but very rarely in other cancer types. This finding helps to explain what makes osteosarcoma such an aggressive form of cancer.

Predicting development

Predicting the likely course of the cancer for patients with osteosarcoma remains an additional major challenge. As part of this study, the team also found a new biological sign in cancer cells that can help to do this, known as loss of heterozygosity (LOH). The researchers found that in osteosarcoma, a high degree of LOH across the genome predicts a lower probability of survival.

“These discoveries go a long way towards improving our understanding of what drives osteosarcoma’s progression and how it may develop in a patient.

“The new insights could, with time, lead to better treatment options and outcomes for patients through more targeted care. The research shows what can be achieved when academia, clinical practice, and the NHS work together and combining research and development efforts across these three streams.”

Greg Elgar

Director of Sequencing R&D at Genomics England and one of the paper’s authors

“We've known for years that osteosarcoma cells have some of the most complex genomes seen in human cancers, but we couldn't explain the mechanisms behind this.

“By studying the genetic abnormalities in different regions of each tumour and using new technologies that let us read long stretches of DNA, we've been able to understand how chromosomes break and rearrange, and how this impacts osteosarcoma disease progression."

Isidro Cortes-Ciriano

Group Leader at EMBL-EBI and co-senior author of the study

“The biomarker could help us identify patients who are unlikely to benefit from treatment which can have very unpleasant effects which patients find difficult to tolerate. This is invaluable for providing patients with more tailored treatments and help spare unnecessary effects of toxic therapies.”

Adrienne Flanagan

Professor at UCL, Consultant Histopathologist at RNOH

The scientists involved in this study would like to thank all the patients and their families who donated samples used in this research.

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