Defining the developmental origin of childhood cancers

Finding the tumor’s cell-of-origin will provide important clues into what has caused its development e.g., a block in differentiation. Relieving such a block pharmacologically would be an attractive therapeutic intervention (so-called maturation therapy).

To find the origin of tumors, we make use of different approaches. First, we apply DNA sequencing technologies to find phylogenetic relations between tumors and normal tissues of the same individual. To do so, we use somatic mutations as “barcodes” to trace back the origin of the tumor. Second, we make use of (single-cell) transcriptome and epigenome sequencing approaches, as we and others have shown that embryonal tumors mirror features of their cells-of-origin to a large extend. By comparing tumor transcriptomes with the transcriptomes of fetal tissue development, we aim to unravel the tumor’s cellular identity.