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

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

In today’s ageing populations, cancer - a degenerative disease - is one of the leading cause of death worldwide and arguably one of the biggest scientific and health challenges of our era. Our bodies are made of millions of billions of small specialised unit blocks called cells. Most cancers arise from one single aberrant cell that has acquired independence and immortality, and embarked on a suicidal mission to grow beyond its tissue constrains to ultimately invade the host body. Because there are so many cell types from which cancer can arise, there are also many different cancer types (e.g. colon, liver, ovarian, prostate, etc.). Sarcomas are cancers arising from the cells of the bone, cartilages and soft tissues (e.g. nerve, muscle) and are a mixed bag of 50-100 different cancer types under the same denomination. Because sarcoma is an uncommon cancer type as a whole, most of these 50-100 sarcoma subtypes are very rare. When we look across cancer genomes, we see recurrent events that distinguish them from most genomes of other “normal” cells in their respective hosts. These events are called somatic driver mutations, which help us understand the cancer’s evolution but also are potential handles for targeted treatments. We now know that the same drivers accumulate across all the “normal” healthy cells in our body, but typically only one or a few cells will lead to cancer. This somatic evolution and in particular somatic evolution leading to cancer is long known but, with the advent of sequencing, we are only starting to characterise it. Ten years ago, the first technologies allowing to sequence single cells have emerged and the field has been exponentially growing ever since. However, these technologies are still expensive, require complex logistics, and come with technical and computational hurdles. Because sarcomas are rare, they require long-term (inter)national efforts to be studied in as much depth as other common cancer types. While these big collection efforts are on going we propose to take a few patients and analyse them in depth using these emerging single-cell technologies. In particular, for this project I set up to study a malignant sarcoma of the soft tissue surrounding our nerves in one patient and perform genome and transcriptome (G&T) sequencing of the same cells. The complexity in the biological questions, the mathematical analyses and the logistics required efforts on various fronts, and I had the chance to participate in several studies where I developed and benchmarked methods to study cancer evolution at the bulk and single cell level; I studied the extent of selection in cancer evolution, and of intra-tumour heterogeneity and chromothripsis - a complex somatic change in the DNA particularly prevalent in sarcomas - across 37 cancer types including sarcomas; I helped characterised the evolutionary landscape of undifferentiated sarcomas; and I analysed single-cell data of sarcoma and leukaemia to better understand the effect of treatment.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз