This action was carried out via 3 work packages (WPs). WP1 comprised the collection, isolation and sequencing of single-cells from a childhood bone cancer, called osteosarcoma, and a childhood muscle cancer called rhabdomyosarcoma. We successfully created single-cell atlases of these two cancer types, fully encompassing the full heterogeneity of these diseases. Using these atlases, we were able to pinpoint exactly where foetal bone and muscle development goes awry and a maturation block occurs within these cancers. These atlases will be available for the sarcoma community upon publication this year in the form of raw sequencing data, gene counts data and a user-friendly website. WP2 involved the collection, isolation and sequencing of normal reference material: embryonic and foetal bone and muscle. Parts of these atlases will be published in 2 publications this year (atlas of the human limb bud and foetal spine, both are currently in review). Lastly, WP3 consisted of the development of computational tools and frameworks to characterize sarcoma single cells and map them on developmental trajectories. One of these tools, alleleintegrator, was published in Communications Biology last year, while the other tools will be published with the larger sarcoma paper this year. This includes a computational framework to identify oncofetal targets – genes that are expressed exclusively during the foetal period and should not be expressed in adult tissues, yet persist in cancers. These are formidable targets for immunotherapies.
This MSCA action has been or will be disseminated in a number of ways, beyond academic publication. The preliminary results of this action were presented at the Gordon Research Conference on single cell biology in May 2021 in Les Diablerets, Switzerland. This action will be presented at the Connective Tissue Oncology Society (CTOS) in November 2023 in Dublin, Ireland. This is the foremost conference for sarcoma specialists in the world. This action provided the data for further grants in this area. The Behjati group has secured funding from Cancer Research UK (CRUK) and Alice’s Arc to further study these childhood cancers. Despite the global COVID-19 pandemic stalling the project and restricting engagement activities, the research fellow engaged in Black STEM futures to support students of Black heritage who are interested in STEM (science, technology, engineering, mathematics and medicine). Thus, results of this MSCA will be reported in forthcoming papers and conferences describing the aberrant developmental trajectories of childhood sarcoma and atlases normal human bone and muscle development. The action has led to further funding to study childhood cancer. The datasets collected during this MSCA will inform and enhance our understanding of paediatrics, oncology, and developmental biology in the coming years.
