The 100,000 Genomes Project

This flagship project to sequence 100,000 genomes of patients affected with cancers and other rare diseases is now closed to recruitment and work has started to analyse the data in the Genomics England Research Environment. This major UK initiative is funded by the National Institute for Health Research, NHS England, The Wellcome Trust, Cancer Research UK and the Medical Research Council. Over 1,000 patients with sarcoma have been recruited from across UK, of which 600 have been recruited from London Sarcoma Service. The UK collection of sarcoma genomes now makes up the largest repository worldwide and will continue to grow as all patients with sarcoma will have access to whole genome sequencing of their tumours from early next year. This is because NHS England has agreed to fund whole genome sequencing of sarcoma from patients across the UK. Dr Fernanda Amary, Consultant Pathologist, is leading and co-ordinating the clinical pathways and implementing this for the London Sarcoma Service.

More information can be found on the Genomics England website https://www.genomicsengland.co.uk/about-genomics-england/the-100000-genomes-project/

GeCIPing Sarcoma

The Sarcoma Genomics England Clinical Interpretation Partnership (GeCIP), led by Professor Adrienne Flanagan of the London Sarcoma Service, brings together sarcoma researchers and clinicians in the UK to process, analyse and interpret the genomics data generated by the 100,000 Genomes Project. Key partners in the genomics working group include scientists from the Francis Crick Institute, University College London,  University of Birmingham and the Wellcome Trust Sanger Institute.

The genomic datasets from sarcoma participants will allow the team to discover genomic mutations (CNVs, SNVs, SVs, indels) contributing to the tumour initiation, development, evolution and intra-tumour heterogeneity. Additional ongoing research studies, led by various Sarcoma GeCIP members, to decipher the transcriptomic and epigenomic landscape of these sarcoma samples from the 100,000 Genomes Project will further contribute to a comprehensive understanding of the recurrent genetic driver mutations in a range of sarcoma subtypes and help to identify and better define the different tumours.

Dr Nischalan Pillay, Honorary Consultant Pathologist at RNOH and Cancer Research UK clinician scientist is a member of the team co-ordinating the analysis of the sarcoma genomes. Dr Pillay’s lab is focussed on unravelling the complex genetics of some sarcoma subtypes for clinical benefit (https://www.ucl.ac.uk/cancer/research/department-pathology/sarcoma-biology-and-genomics). Recently Dr Christopher Steele in the Pillay lab developed a novel method to extract biologically and clinically useful information from the genomes undifferentiated pleomorphic sarcomas which was published in Cancer Cell (https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30097-2). Ms Shadi Hames, a PhD student funded by Sarcoma UK (Sayako Grace Robinson fellowship) will work with Dr Steele to apply this method to the sarcoma genomes sequenced by GEL which has many other sarcoma subtypes. She will also be investigating the genetic determinants of immune evasion in sarcoma which is of clinical importance due to the rapid advances being made in the immunotherapy field.

Tom Prince Osteosarcoma Research Project

The project, led by Prof. Adrienne Flanagan and funded by the Tom Prince Cancer Trust, has contributed enormously to the 100,000 Genomes Project. The funds are being used to generate a comprehensive multi-omic data set for the samples submitted to the 100,000 Genomes Project. These generous funds are also being put towards the purchasing a digital slide scanner and will be based at the Royal National Orthopaedic Hospital. Digital pathology data linked with genetic and clinical data will provide a powerful resource for researchers and clinicians to improve classification of the disease and a greater insight into tumour behaviour.

Improving outcome through Collaboration in OsteosarComa (ICONIC)

The Bone Cancer Research Trust is funding this multidisciplnary cohort study to collect data and samples of all newly diagnosed patients with sarcoma across the UK. This complements and adds value to the Tom Prince Osteosarcoma Research Project and other research projects.

Genomics of Malignant Peripheral Nerve Sheath Tumour (GEM) Consortium 

This philanthropically-funded project is led by Dr David Miller – Boston Children’s Hospital, Harvard. Adrienne Flanagan and Nischalan Pillay and the RNOH pathologists are major contributors to the study which involves an in-depth integrated genetic, transcriptomic and epigenetic data analyses from these neoplasms in order to understand the basic biology of this disease with the aim of identifying prognostic and therapeutic markers.