Publications

Chemotherapy increases the mutation burden of normal blood cells in cancer survivors. Only few drugs damage the DNA directly, while in most patients, chemotherapy-induced mutations are caused by processes similar to those present during normal aging. Cancer Discovery 2022

Antiviral treatment with ganciclovir causes a unique mutational signature in stem cells of human transplant recipients. This signature was also found in therapy-related cancers and can cause cancer driver mutations. Cell Stem Cell 2021

In some children with acute myeloid leukemia, cancer cells have the same amount of DNA changes as healthy blood stem cells. Here, we show that these children have a poorer chance of survival compared to children whose leukemia has an above-average number of DNA changes. This study offers insight into how this form of blood cancer can develop in children. In the future, these findings may help identify which patients have a high-risk form of the disease. Blood Cancer Discovery 2021

Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Nature 2020

Mutation accumulation during life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Using mutations found in in acute myeloid leukemia, we construct a developmental lineage tree of human hematopoiesis, revealing a polyclonal architecture and providing evidence that developmental clones exhibit multipotency. Cell Reports 2018

Here we determine genome-wide mutation patterns in human adult stem cells of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Nature 2016

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