Identifying new diagnostic pathways for unclassifiable sarcomas
Research type
Research Study
Full title
Identifying new diagnostic and treatment pathways for patients with unclassifiable sarcomas
IRAS ID
191091
Contact name
Nischalan Pillay
Contact email
Sponsor organisation
Royal National Orthopaedic Hospital
Duration of Study in the UK
5 years, months, days
Research summary
Soft tissue sarcomas are cancers of connective tissue that occur in ~2500 people a year in
the UK. Up to a quarter of these is not readily classifiable using routine diagnostic methods
and is termed unclassifiable sarcomas or Sarcoma NOS (~ 600 people in 2009- National
Cancer Intelligence Network). This "diagnosis" is based on non-reproducible criteria
resulting in the grouping together of biologically unrelated tumours. This has resulted in poor
interpretability of outcome data from tissue registries resulting in the absence of a cohesive
strategy to better categorise this cohort and a lack of development of therapeutic
approaches.
This study aims to address these inconsistencies by using epi/genomics and transcriptomics rather than morphology which is the status quo. This will entail assessing these tumours against the methylation and mutational profiles of known cancer driver genes and new genomic information from recent sarcoma sequencing studies. This approach is supported by a unique bio-resource of a large cohort of samples from the Royal National Orthopaedic Hospital(RNOH), the informatics expertise in cancer
genome sequencing at the Sanger Institute and the vision of the UCL Cancer Institute to
develop personalised medicine strategies for patients with cancer.AIMS
1) To find biomarkers (genetic or epigenetic) that would assist in a more robust classification of this disease.
2) To identify clinically actionable mutations in UCS that would enable stratification of patients for clinical trials.
3) To identify the epi/genetic drivers of the different subsets of UCS and use these data to investigate the scale of intra-tumoural genetic heterogeneity that may be prevalent in these tumours.2. STUDY OBJECTIVES
Primary objectives:
1) Performing a combination of multiplexed targeted and whole genome sequencing of available UCS to identify the spectrum and nature of somatic events that underpin UCS.
2) Conduct genome wide methylation profiling to determine the extent of DNA methylation in unclassifiable sarcomas compare to other cancers, in particular other sarcoma subtypes.Secondary Objectives:
1) Correlating the genomic findings of UCS to the histological phenotype and clinical outcome in order to determine the genetic attributes that contribute to tumour development and progression.
2) Using established statistical methods to determine the phylogenetic and clonal relationships among driver mutations in UCS that have dedifferentiated from better genetically characterised subtypes5.
3) Utilise the genomic data for identifying diagnostic and treatment strategies for patients with undifferentiated sarcomas by follow-up studies using in-vitro and/or in-vivo techniques.REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
16/NW/0769
Date of REC Opinion
31 Oct 2016
REC opinion
Favourable Opinion