Objetivo 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. Ámbito científico medical and health sciencesclinical medicinesurgerynatural sciencesmathematicspure mathematicsmathematical analysismedical and health sciencesclinical medicineoncologyleukemianatural sciencescomputer and information sciencesartificial intelligencemachine learningnatural sciencesbiological sciencesgeneticsgenomes Programa(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Tema(s) MSCA-IF-2016 - Individual Fellowships Convocatoria de propuestas H2020-MSCA-IF-2016 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-EF-ST - Standard EF Coordinador THE FRANCIS CRICK INSTITUTE LIMITED Aportación neta de la UEn € 195 454,80 Dirección 1 MIDLAND ROAD NW1 1AT London Reino Unido Ver en el mapa Región London Inner London — West Camden and City of London Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 195 454,80
