January 14, 2025 - Vicky Hatch - Osteosarcoma is a type of aggressive bone cancer that most commonly affects children and young adults between the ages of 10 and 20, during times of rapid bone growth. Although rare, 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 to identify what genetic mutations drive the disease. As a result, there has been little advancement in treatment options over the past 40 years.
New research, published in the journal Cell, solves the mystery of what drives the genomic rearrangements causing the aggressive development and evolution of osteosarcoma tumours. By analysing the largest collection of whole-genome data from osteosarcoma patients, the researchers identified a new mutation mechanism, called loss-translocation-amplification (LTA) chromothripsis, which is present in approximately 50% of high-grade osteosarcoma cases.
This finding explains the unique biology that makes this tumour type so aggressive and the high levels of genomic instability observed in osteosarcoma cancer cells. The study also presents a prognostic biomarker – a biological characteristic of cancer cells that can help predict patient outcome – that might be used to anticipate the likely course of the disease.
This work is a collaboration between researchers at EMBL’s European Bioinformatics Institute (EMBL-EBI), University College London (UCL), the Royal National Orthopaedic Hospital, and the R&D laboratory of Genomics England.
“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,” said Isidro Cortes-Ciriano, Group Leader at EMBL-EBI and co-senior author of the study. “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.”
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