Genetic Marker Indicates Benign from Aggressive Bone Tumours

Scientists from the Francis Crick Institute, the Wellcome Sanger Institute and University College London Cancer Institute have discovered the first genetic marker for the bone tumour, osteoblastoma.

Whole-genome and transcriptome sequencing of human bone tumours revealed that a genetic change that affects the transcription factor, FOS, is a hallmark mutation of osteoblastoma and results from the studies* will help clinicians correctly distinguish benign osteoblastoma tumours from aggressive osteosarcoma tumours and direct the correct treatment.

Osteoblastoma is the most common benign tumour of the bone, mainly affecting children and adults between the ages of 10 and 25. It is treated by surgical removal of the tumour, however the diagnosis of osteoblastoma can be challenging. Under the microscope, osteoblastoma tumours can look very similar to osteosarcoma, an aggressive form of bone cancer that requires extensive treatment, sometimes including amputation or significant surgery and chemotherapy.

Matthew Fittall, co-first author of the paper and postdoc in the Cancer Genomics Lab at the Crick said: "We have known for a while that FOS is involved in the progression of bone tumours, however we have not found mutations of FOS in human bone-forming tumours before. Using genomic sequencing we have shown that mutations in FOS and its relative FOSB are diagnostic markers of osteoblastoma."

Sam Behjati, co-lead author from the Wellcome Sanger Institute and University of Cambridge, said: "The main clinical challenge when diagnosing osteoblastoma can be to reliably distinguish these tumours from osteosarcoma. These two forms of bone tumour require very different treatments: osteoblastoma tumours just need removing to ease symptoms, whereas osteosarcomas is treated aggressively with surgery and intensive chemotherapy. For the first time, we have discovered a specific mutation that defines osteoblastoma."

Professor Adrienne Flanagan, co-lead author from the University College London Cancer Institute and Royal National Orthopaedic Hospital NHS Trust, said: "Genomics is transforming our understanding of cancers. Our discovery of the genetic mutation that characterises osteoblastoma will help clinicians diagnose it with more confidence and direct the correct treatment."

*The research paper 'Recurrent rearrangements of FOS and FOSB define osteoblastoma' is published in Nature Communications