UCL Cancer Institute

Genetics and Cell Biology of Sarcoma

Group Leader: Professor Adrienne M Flanagan

The research performed by this group is intimately related to the clinical service provided at The Royal National Orthopaedic Hospital and University College Hospital (The London Bone and Soft Tissue Sarcoma Service) which is one of the largest sarcoma units in Europe.

Sarcoma is a rare group of tumours that represent less than 2% of all cancers. These tumours are genetically subdivided in two groups, those which harbour a hallmark translocation as seen in synovial sarcoma, PNET/Ewing sarcoma, liposarcoma, and those with a more complex karyotype such as osteosarcomas.

 
Chordoma: A light photomicrograph of a chordoma showing the characteristic findings of cords of polygonal cells set within a mucoid matrix.

Research Interests

Adrienne M Flanagan

Genetics and cell biology of sarcoma with a major focus on osteosarcoma, chordoma and peripheral nerve sheath tumour.

Nadege Presneau

Genetics and cell biology of sarcoma with a major focus on osteosarcoma, chordoma and peripheral nerve sheath tumour.

Partnerships

Sarcoma research is performed at UCL-Cancer Institute in partnership with the national specialist clinical service provided by The London Sarcoma Service at The Royal National Orthopaedic Hospital and University College Hospital. This is one of the largest sarcoma units in Europe.

Sarcomas

Sarcomas are malignant tumours of the musculoskeletal system 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 available for research. The focus of the research is to refine the classification of disease, and to identify biomarkers for prediction for both response to therapies, and clinical outcome. The technologies employed include genomic analysis (gene expression microarray, microRNA) siRNA, primary cell culture and molecular biology.

Osteosarcoma

The most common primary malignant bone tumour is a disease that affects all ages but predominantly teenagers and adolescents. The aim of this work is to identify biomarkers which will predict response to therapy, and clinical outcome.

Funding: Skeletal Cancer Action Trust, Bone Cancer Research Trust and The Pathological Society of Great Britain and Ireland

 
Intense positive nuclear staining for brachyury in chordoma.

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. Having shown that this tumour expresses brachyury (Henderson et al., 2005; Vujovic et al., 2006; Tirabosco et al. 2007), a crucial transcription factor, both necessary and sufficient for mesoderm formation, we are studying its role in the development and progression of chordoma in collaboration with Professor Claudio Stern, Department of Cell and Developmental Biology, UCL.
We are working closely with the Wellcome Trust Sanger Centre and the Chordoma Foundation so that whole genomic analysis of chordomas can be achieved which should reveal all the genetic abnormalities in this tumour and potentially lead to therapeutic targets.

The research is funded by the Rosetrees Trust. The Chordoma Foundation has funded us to generate chordoma cell lines because the lack of primary tumours and immortalised cell lines hampers the ability to study this disease. We hope that the availability of cell lines will allow the data generated from the genomic analysis in the Sanger Institute to be exploited rapidly for patient benefit.

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). We are collaborating with Stefan Beck, Professor of Medical Genomics, in the study of methylation of nerve sheath tumours.