Sarcomas are rare cancers, accounting for just 1% of cancers. There are about 3,500 cases a year in the UK. Sarcomas can occur at almost any site in the body, meaning they are challenging to diagnose and treat. Sarcoma patients are often diagnosed late, and so have poor clinical outcomes compared to people with common cancer types – something that has improved little since the 1980’s.
Sarcomas are among the most diverse cancer types. There are more than 100 known subtypes. They are usually treated in a small number of specialist units. This means there is often good sample and data collection, and standardised quality of care. Soft tissue sarcomas, although more common, are also treated in a limited number of units.
Data from sarcoma participants in the 100,000 Genomes Project will help to identify and better define the different tumours – based on the genetics, appearance and response to treatment.
|SUBDOMAIN||SUBDOMAIN LEAD/S||RESEARCH DESCRIPTION|
|Optimal samples, pathology, consent and clinical data||Prof. Jeys, Mr. Gerrand, Dr. Pillay, Prof. Hassan, Prof. Judson||Samples and consent taken from the London Sarcoma Service, Royal Marsden NHS Trust (RMH), Oxford Sarcoma Service, Birmingham, Newcastle. Including frozen sarcoma samples with matched normal tissue, plasma, germ line DNA and annotated clinical metadata.|
|Building capacity in bioinformatics||Prof. Campbell, Prof. Luscombe, Prof. Balloux, Dr. Herrero||The Bill Lyons Informatics Centre, headed by Dr. Herrero will provide bioinformatics expertise in the processing and analysis of the different -‐omics data. The team will contribute to the analysis of SNVs, CNAs and other somatic aberrations from the genome sequences. Further research proposals will be based on relating these genomic data to additional data including epigenomics (Prof. Beck) and compare the somatic mutations from the samples with the ctDNA and single cell genomic sequences. Lastly, they will work on the statistical models to integrate clinical imaging data, namely x-‐rays, MRI and CT scans (with Prof. Luscombe). The Bill Lyons Informatics Centre is supported by the UCL CRUK Centre grant and will use the MRC-‐funded eMedLab computational infrastructure for developing new analysis pipelines and integrative models. Prof. Campbell and his team will assist with expertise in gold-‐standard variant and driver annotation and in developing models to integrate the disparate –omics datasets. Prof. Balloux’s research will focus on characterising “blood microbiomes” and searching for cryptic pathogens from non-‐human reads. His team also has expertise in bioinformatics and computational biology on human genomes. As such, they can also contribute to the core analyses that may be of more immediate interest to other members of the domain.|
|Epigenetics, circulating tumour cells, circulating DNA and single cell sequencing||Prof. Beck, Prof. Voet, Dr. Van Loo, Dr. Forshew, Dr. Rankin||Prof. Beck: Despite large sequencing efforts in cohorts of bone sarcoma (ICGC) it has been identified that a substantial number of cases still show no recurrent genetic driver mutations. There is therefore a strong argument for investigating the epigenetics of these tumours. Prof. Flanagan has an on-‐going collaboration with Prof. Beck (Epigenetics) at UCL who will support our genomics effort with analysis and the expertise of his group should this sarcoma GeCIP obtain funding.
Dr. van Loo and Prof. Voet: Molecular archaeology of sarcoma: inferring intra-‐tumour heterogeneity and timelines of cancer development and evolution.
Dr. Forshew: It is now well established that many solid tumours release DNA into the circulation. Dr Forshew was part of the team that first demonstrated non-‐invasive solid tumour mutational profiling by direct sequencing of this circulating tumour DNA (ctDNA). Prof. Flanagan and Dr Forshew have demonstrated for the first time that a range of sarcoma including osteosarcoma, chondrosarcoma and giant cell tumour of bone release mutant DNA into circulation (unpublished findings).
Dr. Rankin is leading a multicentre trial in Newcastle investigating the detection of circulating tumour cells.
|Training Group||Prof. Luscombe, Prof. Flanagan, Dr Van Loo,|
Prof. Campbell, Prof. Jeys, Prof. Shipley
|Dr. Behjati through his PhD in cancer genomics has contributed significantly to the delivery of the ICGC bone sarcoma project at the Sanger Institute. Dr’s Pillay (PhD) and Mifsud (PhD) are histopathologists who have both spent training time at the Sanger Institute on the bone sarcoma project and will continue developing these skills as part of the Sarcoma GeCIP. Dr’s Parry and Ford are surgical trainees with research interests in sarcoma.|
|Molecular tumour||Prof. Flanagan, Prof. Shipley, Prof. Campbell||Key function: Building capacity and experience in the identification of actionable mutations, correlation with histopathology, radiology, development of clinical trials and clinical outcome data and monitoring.|
|Paediatric sarcoma||Prof. Flanagan, Prof. Shipley, Dr. Chisholm||Sarcomas are rare, aggressive tumours with unmet need that frequently affect the young. This sub-group of the sarcoma GeCIP aims to collaborate with the paediatric sarcoma subdomain as young patients with these tumours are of mutual interest with implications for both domains in terms of molecular diagnosis, research and treatment. Prof. Flanagan is represented in the paediatric sarcoma domain.|