Why do certain individuals develop cancer and others don’t? And why do children get cancer? Our vision is that by studying mutations in normal cells, we obtain insight into the etiology of cancer. We think this knowledge is crucial to improve cancer diagnostics and treatment, as well as for developing preventive strategies.

On the origin of cancer: studying somatic evolution in normal tissues

Identifying the rate limiting steps of cancer initiation in human tissues is challenging as many factors can play a role. The mutations in the genomes of cells can serve as an archive of their life history. We aim to decode these archives in order to pinpoint the initiation of cancer and identify causal processes in human tissues. To study the etiology of cancer, we have 3 research themes in our lab.

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Theme 1: Tissue-specific mutation accumulation in human stem cells

Organ-specific cancer incidence varies significantly throughout the human body, which cannot be solely explained by different exposures to mutagenic environmental. Adult stem cells are likely the cellular targets for accumulation of pre-cancerous successive oncogenic hits, which eventually can give rise to tumor development, owing to their life-long capacity to propagate mutations to both self-renewing progeny and downstream progenitors. We aim to identify and study the mutational processes that are active in adult stem cells of various organs and precede oncogenic transformation.

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Theme 2: Tracking the origin of cancer

DNA is the largest biomolecule in the cells, which unlike other biomolecules is irreplaceable. The processes causing mutations leave characteristic patterns in the DNA, which can serve as a functional readout of mutagenic and/or DNA repair activity. In addition, phylogenetic relationships between different cells of the same individual can be exploited measure clonal dynamics within tissues. We aim to identify and study the mechanisms underlying characteristic mutation patterns in cancers as well as use mutations to retrospectively trace the cellular origin of cancer.

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Theme 3: The etiology of therapy-related malignancies in cancer survivors

Most chemotherapeutic drugs act by fatally damaging the DNA or blocking the replication thereof. However, noncancerous cells are also damaged by treatment, which can result in the accumulation of DNA mutations in normal tissues with potentially adverse effects later in life, such as novel malignancies. Our goal is to study the mutational effects of cancer treatment in normal tissues of children in order to develop novel treatment strategies aimed at minimizing or preventing adverse late effects.

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