Osteosarcoma (OS) is type of bone tumour that mostly affects children and young adults. Survival rates have improved little over the past four decades and it is still poorly understood how the disease develops and spreads. Dr Sam Behjati and his team will analyse the gene activity of growing and spreading OS cells to identify key targets for the development of effective new treatments and more accurate monitoring techniques.
Developmental states of localised and metastatic osteosarcoma cells – a knowledge bank for novel biomarkers and therapeutic approaches
Dr Sam Behjati
Wellcome Sanger Institute
Cambridge, CB10 1SA
14 December 2020
Osteosarcoma (OS) is the most common type of bone tumour in children and young adults. It is caused by the abnormal growth of bone cells. Only around 65% of children with OS survive for five years or more and survival rates are much lower if the cancer has spread to other parts of the body. Sadly, diagnosis of OS is often delayed and survival outcomes for patients have made little improvement over the past four decades. Furthermore, we still can’t predict at diagnosis which patients could be cured with surgery alone and which patients cannot currently be cured, even with chemotherapy. A better understanding of how OS grows and spreads could reveal targets for the development of effective new treatments. It could also provide clues to help doctors monitor the disease more closely in patients and provide a more accurate prognosis.
OS seems to be associated with bone growth spurts during puberty. Dr Sam Behjati and his team are investigating how healthy growing bone cells transform into OS cells by comparing their gene activity. In healthy cells, genes can be “switched on” or “switched off” over time depending upon their job. Making sure that the right genes are switched on or switched off at the right time is essential for normal cell functioning. It’s increasingly understood that many diseases are caused by or associated with genes behaving incorrectly.
Dr Behjati and his team will analyse the gene activity in OS cells by sequencing their messenger RNA (mRNA) from both localised tumours and tumours that have spread to other parts of the body. Genes produce mRNA when they are active, which codes the production of different proteins. Dr Behjati’s team will then compare this activity to normal gene behaviour in healthy growing bone cells. The differences in gene activity could provide key clues as to what triggers healthy cells to turn into OS cells, and then what triggers those OS cells to spread.
It is not well understood how OS first develops or what then causes it to spread to other parts of the body. By analysing how gene activity changes as OS progresses, Dr Behjati and his team could help to identify targets for the development of new treatments to halt the growth and spread of the disease. Their research could also yield valuable clues to help doctors monitor the disease more accurately in patients and tailor treatments accordingly.
This project is led by Dr Sam Behjati, in collaboration with Prof. Adrienne Flanagan. Dr Behjati is a Group Leader at the Wellcome Sanger Institute, which hosts one of the world’s largest single cell RNA sequencing facilities. His group has extensive experience in analysing cancer single cell data and pioneered the approach of cancer-to-normal-cell comparisons to reveal the developmental state of cancers.
Prof. Flanagan is a clinical pathologist at the Royal National Orthopaedic Hospital. Both Dr Behjati and Prof. Flanagan have collaborated for over eight years to study OS and other bone and soft tissue tumours. Together they have conducted many of the pivotal genetic studies of such tumours, some of which have changed clinical practice. This project represents a cutting-edge experiment which few groups globally would be able to deliver.