Published on: 18th February 2025
Osteosarcoma is the most common primary bone cancer in children and young adults. Introduction of chemotherapy to the treatment regime in the 1980s dramatically changed survival of those affected by this aggressive disease. However, improvements in survival and understanding why this disease can behave in such manner has since been disappointing.
The RNOH and UCL pathology team at RNOH, led by Professor Adrienne Flanagan including consultant pathologists, Dr Fernanda Amary and Dr Roberto Tirabosco 
(pictured right) joined forces with Dr Isidro Cortes-Ciriano, Group Leader at EMBL-EBI and co-senior author of the study, to undertake the analysis of the largest genomic study of osteosarcoma ever done. Using the most advanced sequencing technology and analysis, the new study, published in the Journal Cell, solves the mystery of what drives the rapid growth in about 50% of osteosarcoma. The new mutation mechanism is called loss-translocation-amplification (LTA) chromothripsis, which is present in approximately 50% of high-grade osteosarcoma cases.
Apart from providing new insights into the biology and behaviour of this rare disease, they have also made advances in predicting the likely course of osteosarcoma, which is a major unmet need because at present, it is not possible to predict which patients are likely to survive. The findings of a high level of loss of heterozygosity (LOH) could help to predict survival probability.
However, none of this research would have been possible without the generous, selfless contribution of patients and their families over the last two decades. Even when patients and their families are coming to terms with the news of their frightening diagnosis, they so often think of others and donate their tissue, surplus to diagnostic requirement, for research purposes. When studying rare tumours, such as osteosarcoma, this generous act makes research possible. It brings about change, providing opportunities to improves the lives of so many. This research published in Cell demonstrates the power of research. .
The values of the Trust include ‘excellence, in all we do, and ‘patients always come first’ and the RNOH sarcoma multidisciplinary team including pathologists, surgeons, radiologists, nursing team and our mangers consider that research is required to deliver these values. We are privileged to be a specialist Sarcoma Service in England; if we cannot improve the lives of patients with sarcoma – who can?
Professor Adrienne Flanagan (right), co-senior author of the study from UCL Cancer Institute and a Consultant Histopathologist at RNOH, said: "Our results have the potential of changing the clinical management of osteosarcoma by selecting those patients that are more likely to benefit from chemotherapy. These drugs have very unpleasant side effects and can be poorly tolerated by patients."
Dr Solange De Noon, co-first author of the study from RNOH, UCL Cancer Institute and EMBL-EBI, regularly travelled across these three sites. Such commitment and dedication to research with the aim of improving patients’ care is what allowed this study to be accomplished.
Solange (left) said “Our work to uncover a key biological mechanism that drives osteosarcoma and gain insight into how a patient’s disease is likely to behave represents a significant achievement for osteosarcoma research, especially after four decades where diagnosis and treatment haven’t seen significant progress. Overall, this research should lead to provision of more tailored treatments and help to spare them from unnecessary side effects of toxic therapies.”
This research is dedicated to Tom Prince, a young patient at RNOH, and who died of osteosarcoma. The Tom Prince Cancer Trust was set up by his family in 2004 to raise funds for research into osteosarcoma.
The research used data from the 100,000 Genomes Project, a pioneering study led by Genomics England and NHS England that sequenced whole genomes from NHS patients affected by rare conditions or cancer.
This work was a collaboration between researchers at RNOH, EMBL’s European Bioinformatics Institute (EMBL-EBI), University College London (UCL), and the R&D laboratory of Genomics England.