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UCL Cancer Institute

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Genetics and Cell Biology of Sarcoma

Group Leader: Professor Adrienne Flanagan

Research Interests

This team studies the genetics and cell biology of sarcoma – tumours of bone and soft tissue.

Sarcomas

Sarcomas are malignant tumours of the musculoskeletal system (bone and soft tissue) representing less than 2% of all cancers. However, the centralisation of the treatment of these tumours in the London Sarcoma Unit allows basic and clinical research to succeed. We have a large biobank of these rare tumours collected for over a decade which has allowed us play a central role in identifying the genetic alterations in these tumours.

The focus of the research is to refine the classification of bone and soft tissue tumours using molecular markers, and to identify biomarkers for prediction for both response to therapies, and clinical outcome.

We are currently going through a rapid phase of discovery whereby the genetic alterations in bone and soft tissue tumours are being catalogued. The next phase of the research will be to interrogate these genetic alterations. This will require the development of new models of disease in which the genetic alterations, alone and in combination, can be studied in order to determine their significance in terms of tumour growth and behavior, but also to determine how these induce resistance to conventional chemotherapy and new targeted treatments.

Research Projects

Chordoma

A rare locally aggressive malignant bone tumour, arises in the vertebral bodies, and shows notochordal differentiation. We have one of the largest chordoma tumour banks available for research purposes. We reported that this tumour expresses brachyury (Henderson et al., 2005).

We have generated 4 new chordoma cell lines which we are now screening against 1000 compounds to identify new therapies for this disease.

Chondrosarcoma

This is the second most common primary malignant bone tumour. We were the first to report that ~60% of these cancers have a mutation in the gene IDH1, and that this mutation is the cause of Ollier Disease and Maffucci syndrome. In collaboration with the Wellcome Trust Sanger Institute we have recently undertaken genome sequencing of ˜80 chondrosarcomas (manuscript in press).

The next phase of this research is to determine the significance of these genetic alterations both alone and in combination.

Osteosarcoma

The most common primary malignant bone tumour is a disease that affects all ages but predominantly teenagers and adolescents. It is a heterogeneous disease, both morphologically and genetically. Conventional chemotherapy was introduced as part of treatment for this disease in the 19080 when it dramatically improved outcome to approximately 60% survival over 5 years. However, there has been little advance made since that time.

A large number of our tumours is currently undergoing genomic sequencing in the Wellcome Trust Sanger Institute as part of the International Cancer Genome Consortium and it is hoped that this will provide insight into this complex disease and allow the development of new treatments. 

Nerve sheath tumours

Nerve sheath tumours arise from the cells around nerves. Benign nerve sheath tumours (schwannomas and neurofibromas) and malignant (malignant peripheral nerve sheath tumours – MPNST) occur rarely in the general population and commonly in individuals with a disease known as neurofibromatosis type 1. This project is working towards identifying a molecular signature which could distinguish easily between benign and malignant nerve sheath tumours and identifying therapeutic targets for the treatment of malignant disease (Parrinello S et al., 2008; Presneau 2012). We are collaborating with Stefan Beck, Professor of Medical Genomics, in the study of methylation of nerve sheath tumours.

 

Last updated: May 2018