Project description
Evolution of childhood sarcoma
Although cancer in children is rare, the spectrum of cancers reflects the way children’s bodies change at the cellular level. The EU-funded CAtS project will focus on bone and soft tissue cancers (sarcomas), which represent nearly 21 % of cancers in children. Using single-cell RNA sequencing, scientists will analyse childhood and adult sarcomas and compare results with corresponding normal tissue. This will provide insight into cancer cell biology and the transcriptional alterations responsible for malignant transformation in children compared to adults. The generated map of mutations and expression profiles of normal bone and cartilaginous tissue will serve as the basis for future research on the clonal evolution of sarcoma.
Objective
Each year more than 35,000 European children and young people are diagnosed with cancer. Childhood cancer remains a major public health and socioeconomic issue in Europe and around the world. Cancer arises when a single cell transforms and divides uncontrollably, resulting in a malignant mass of tumour cells. To study cancer, we must understand how these normal cells change. Our current understanding of how normal cells vary across the many tissues of our body is poorly understood. Child development represents a unique challenge in understanding our cells, as children’s bodies change at a cellular level entirely different than adults. This is reflected in the spectrum of cancers diagnosed in children compared to adults, particularly in bone and soft tissue cancers (sarcomas) where they present in less than 1% of adults' cancers and nearly 21% of children's cancers.
With the advent of high-throughput single-cell RNA sequencing (scRNA-seq), it is now possible to analyze cell populations at remarkable scale and resolution. The primary purpose of this project is to use scRNA-seq to reconstruct the phylogenetic cellular lineage of childhood and adult sarcomas, and corresponding normal tissue. This fellowship aims to (1) discover and define differences between normal and cancer cell biology at single-cell resolution and (2) use machine learning to determine the cell type (cell-of-origin), the somatic changes and transcriptional trajectories of normal cells that lead to malignant transformation in children compared to adults.
This project represents the highest resolution map of the intratumour genetic heterogeneity and clonal evolution of sarcoma ever produced. Another outcome of this project will be a reference map of all of the somatic mutations and expression profiles of normal bone and cartilaginous tissue. This will be a pivotal resource for the global research community - the ‘Bone’ and ‘Cartilage’ branches of the ‘Developmental Human Cell Atlas’.
Fields of science
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
CB10 1SA SAFFRON WALDEN
United Kingdom