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SIngle-cell multi-OMICs approach to study intra-tumour heterogeneity of soft tissue Sarcomas

Objective

Recently, multi-omics approaches have led to a plethora of publications describing in detail the ‘omics landscapes of common cancer types. However, at the bulk tissue level, integrating different ‘omics layers remains an uncompleted challenge. Soft tissue sarcomas are rare and often aggressive cancers of mesenchymal origin representing ~1% of all cancers but encompassing at least 50 subtypes. Hence, collecting enough of these rare samples for significant findings in a timely fashion is the biggest hurdle. This issue can be addressed by repeating observations within individual patients to generate new hypotheses. Our long-term collaboration aims to obtain the genome, transcriptome and methylome of each of 1,000 single-cells from 10 individual subtypes of soft tissue sarcomas. This design is possible thanks to DNA & RNA single-cell sequencing (SCS) of the same cell in Dr. Voet’s lab, and bespoke computational analyses in Dr. Van Loo’s lab, and access to this rare material of Prof. Flanagan, lead for the sarcoma component of the Genomics England 100,000 Genomes Project. This proposal is the pilot project, where we focus on one malignant peripheral nerve sheath tumour, a rare aggressive cancer originating from the connective tissues surrounding nerves. We will also sequence multiple regions of the primary tumour, the blood, and cell-free tumour DNA (ctDNA) before surgery and subsequently every three months. Prof. Flanagan’s group will process the samples, and Dr. Voet will oversee the sequencing. In Dr. Van Loo’s lab, I will develop the computational tools to uncover the 3 ‘omics signals at the single-cell level that are averaged out in bulk tissues. SCS will shed light on the fundamental links between cancer genomic subclones and the transcriptional and epigenetic diversity of cancer cell types; and we will answer whether ctDNA reflects the diversity of cancer cells and how it evolves in the course of treatment.

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2016

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Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 195 454,80
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NW1 1AT London
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Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 195 454,80
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